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.

ObjectiveTo investigate the trend and influencing factors of newly reported human immunodeficiency virus (HIV) positivity rate among men who had sex with men (MSM) in Shanghai from 2021 to 2024, and to provide evidence for formulating scientific prevention and control measures of AIDS. MethodsMultiple rounds of cross-sectional questionnaire surveys were conducted among MSM by Shanghai Qing’ai Health Promotion Center. Pearson and Cochran-Armitage trend χ² tests were used to analyze the differences and changes in population characteristics and newly reported HIV positivity rates. A logistic regression model was applied for multivariate analyses of factors associated with newly reported HIV positivity. ResultsA total of 1 653 MSM who had not been previously diagnosed with HIV infection were surveyed. The newly reported HIV positivity rates in 2021, 2023, and 2024 were 7.87%, 3.91%, and 3.06%, respectively, showing a decreasing trend (χ²_trend=13.460, P_trend<0.001). Multivariate analyses revealed that MSM aged 18‒<25 years, residing locally for <1 year, identifying as bisexual, lacking HIV knowledge, and having ≥10 same-sex partners in the past 6 months exhibited higher newly reported HIV positivity rates. Conversely, MSM knowledgeable about HIV prevention, residing locally for 1‒5 years, and engaging in oral sex with male partners in the past 6 months demonstrated lower HIV positivity rates. Annual analyses revealed that MSM with HIV knowledge had lower newly reported HIV positivity rates in 2023 and 2024 (aOR=0.300, 95%CI: 0.811‒0.111; aOR=0.202, 95%CI: 0.085‒0.483). ConclusionThe newly reported HIV positivity rate among MSM in Shanghai from 2021 to 2024 showed a decline. Future interventions should focus on young and mobile MSM, strengthen HIV knowledge education through platforms such as the internet, promote safe sexual behaviors and regular testing, and further expand the coverage of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) to control HIV transmission within this population.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

BACKGROUND: Modern acupuncture anesthesia is a combination of Chinese and Western medicine that integrates the theories of acupuncture with anesthesia. However, some clinical studies of acupuncture anesthesia lack specific descriptions of randomization, allocation concealment, and blinding processes, with subsequent systematic reviews indicating a risk of bias. OBJECTIVE: Clinical trial registration is essential for the enhancement of the quality of clinical trials. This study aims to summarize the status of clinical trial registrations for acupuncture anesthesia listed on the World Health Organization International Clinical Trials Registry Platform (ICTRP). SEARCH STRATEGY: We searched the ICTRP for clinical trials related to acupuncture anesthesia registered between January 1, 2001 and May 31, 2023. Additionally, related publications were retrieved from PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data. Registrations and publications were analyzed for consistency in trial design characteristics. INCLUSION CRITERIA: Clinical trials that utilized one of several acupuncture-related therapies in combination with pharmacological anesthesia during the perioperative period were eligible for this review. DATA EXTRACTION AND ANALYSIS: Data extracted from articles included type of surgical procedure, perioperative symptoms, study methodology, type of intervention, trial recruitment information, and publication information related to clinical enrollment. RESULTS: A total of 166 trials related to acupuncture anesthesia from 21 countries were included in the analysis. The commonly reported symptoms in the included studies were postoperative nausea and vomiting (19.9%) and postoperative pain (13.3%). The concordance between the publications and the trial protocols in the clinical registry records was poor, with only 31.7% of the studies being fully compatible. Inconsistency rates were high for sample size (39.0%, 16/41), blinding (36.6%, 15/41), and secondary outcome indicators (24.4%, 10/41). CONCLUSION The volume of acupuncture anesthesia clinical trials registered in international trial registries over the last 20 years is low, with insufficient disclosure of results. Postoperative nausea and vomiting as well as postoperative pain, are the most investigated for acupuncture intervention. Please cite this article as: Li Y, Liu YN, Guo Z, Gu ME, Wang WJ, Zhu Y, Zhuang XJ, Chen LM, Zhou J, Li J. Current situation of clinical trial registration in acupuncture anesthesia: A scoping review. J Integr Med. 2025; 23(3): 256-263.
Humans ; Acupuncture Analgesia ; Acupuncture Therapy ; Anesthesia ; Clinical Trials as Topic ; Registries

Objective To investigate the impacts of wogonin on cardiac inflammation in pregnant hypertensive rats by regulating the monocyte chemotactic protein-1(MCP-1)/CC chemokine receptor 2(CCR2)signaling pathway.Methods Pregnancy hypertensive rat model was established by intragastric administration of nitroso L-arginine methyl ester.The rats were randomly divided into control group(0.9％NaCl),model group(0.9％NaCl),experimental-L,-H groups(3.33 and 13.32 mg·kg-1 Wogonin),magnesium sulfate group(intrabitoneal injection 100 mg·kg-1magnesium sulfate),recombinant rat MCP-1 protein(rRMCP-1)group(intraperitoneal injected 0.026 mg·kg-1 rRMCP-1),experimental-H+rRMCP-1 group(gavage 13.32 mg·kg-1 Wogonin+0.026 mg·kg-1 rRMCP-1),each group consisted of 12 animals.Each group was administered once a day for 7 days.The serum levels of tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay;the expression of M1 and M2 macrophages in rat myocardium was detected by immunofluorescence staining;the expression of MCP-1 protein in rat myocardium was detected by Western blot.Results Serum TNF-α levels in control group,model group,experimental-L,-H groups,magnesium sulfate group,rRMCP-1 group,experimental-H+rRMCP-1 group were(10.06±0.41),(23.39±0.57),(19.89±0.62),(13.64±0.51),(12.97±0.48),(28.84±1.05)and(17.15±0.69)pg·mL-1;the fluorescence intensities expressed by M1 type macrophages were 32.26±1.43,58.84±2.11,50.66±1.89,36.69±1.57,35.87±1.59,67.73±2.01 and 48.53±1.86;the fluorescence intensities expressed by M2 type macrophages were 31.15±1.20,46.56±1.03,51.92±1.04,59.11±0.82,59.26±0.83,40.26±1.12 and 45.53±1.65;the expression of MCP-1 protein were 0.58±0.03,1.86±0.11,1.62±0.09,0.76±0.07,0.78±0.06,2.16±0.13 and 1.34±0.12,respectively.The above indicators in the model group were compared with those in the control group,compare the above indicators with the model group in the experimental-L,-H groups,magnesium sulfate group and rRMCP-1 group,the above indicators in the experimental-H group were compared with those in the experimental-H+rRMCP-1 group,the differences were statistically significant(all P＜0.05).Conclusion Wogonin may inhibit cardiac inflammatory response in pregnant hypertensive rats by inhibiting the MCP-1/CCR2 signaling pathway.

OBJECTIVE To investigate the transcriptomal charactersistics of the striatum in the chronic social defeat stress(CSDS)model mice by using spatial transcriptome analysis and to address the underlying mechanism of the striatum in regulating depressive states.METHODS The CSDS para-digm was employed to establish a depression-like mouse model.The depressive indicators of behavioral despair,anhedonia,and social disorders were assessed through a battery of tests,including the tail suspension test,forced swim test,sucrose preference test,and social interaction experiments.The control mice and the mice exhibiting CSDS-sensitive depression-like behaviors were selected for spatial tran-scriptome sequencing of the striatal region.This sequencing aimed to identify highly expressed genes,followed by KEGG and GO enrichment analyses using the DAVID database.RESULTS The CSDS mouse model effectively induced behavioral despair,anhedonia and social avoidance(P<0.05,P<0.01).Spatial transcriptome analysis revealed 193 differentially expressed genes in the striatum of normal mice.KEGG and GO analyses indicated that these genes were primarily associated with striatal devel-opment,locomotor behaviors,and drug addiction.They were strongly implicated in signaling pathways such as cyclic adenosine monophosphate,cyclic guanosine monophosphate-protein kinase G,calcium signaling,Ras-related protein 1,and mitogen-activated protein kinase,and synaptic linked to GABAergic and dopaminergic neurons.In contrast,CSDS modeling mice led to the identification of 298 differentially expressed genes in the striatum compared with the normal control mice.These genes were significantly enriched in pathways related to neurodegenerative diseases,including Huntington disease,Alzheimer disease,and Parkinson disease.CONCLUSION Depressive states induced by CSDS are associated with the pathological processes underlying neurodegenerative diseases in the striatum.

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 summarize the key prenatal ultrasound diagnosis features of Apert syndrome, analyze the causes of missed diagnosis and misdiagnosis, and propose corresponding preventive strategies.Methods:A retrospective analysis was made on the medical records and prenatal ultrasound images of 15 fetuses (including 14 cases referred from other hospitals) who underwent prenatal ultrasound examination in Guangdong Women and Children Hospital from August 2014 to May 2022 and were eventually clinically confirmed as Apert syndrome by induction or after birth. By conducting a comparative analysis, particularly focusing on the initial and final diagnoses of referral cases, the key ultrasound diagnostic points of Apert syndrome and the causes for missed and misdiagnosis were summarized.Results:①Diagnostic accuracy: Among the 15 fetuses, 11 cases (73.3%) were correctly diagnosed by prenatal ultrasound and 4 cases (26.7%) were missed diagnosis and misdiagnosis. For the 14 referral cases, only 2 cases (14.3%) were correctly identified in the initial diagnosis at the referring hospital (14.3%), and 12 cases (85.7%) were missed missed diagnosis and misdiagnosis. ②Detection rate of ultrasound signs: In the 15 fetuses with Apert syndrome, the detection rate of " cloverleaf" skull was 13.3% (2/15), premature coronal suture was 66.7% (10/15), the " brain shadowing sign" and flat occiput were both 93.3% (14/15), prominent forehead, hypertelorism and bilateral syndactyly of hands were all 100% (15/15), and bilateral syndactyly of feet was 73.3% (11/15). ③Analysis of missed diagnosis and misdiagnosis: Among the 4 cases of missed diagnosis and misdiagnosis in our hospital, premature closure of coronal suture, " brain shadowing sign", flat occiput and hypertelorism were all not recognized. Among these, 3 cases also missed the prominent forehead, bilateral syndactyly of hands and feet. Additionally, 1 case of bilateral syndactyly of hands was misdiagnosed as partial absence of metacarpals and phalangess.Conclusions:In the prenatal ultrasound diagnosis of fetal Apert syndrome, the symmetric syndactyly of both hands serves as an extremely important diagnostic clue. The " cloverleaf" skull is not common. The premature closure of coronal suture as a direct diagnostic sign with a high detection rate, highlighting its significance in the diagnostic of Apert syndrome. Furthermore, the high detection rates of characteristic ultrasound features such as prominent forehead, flat occiput, " brain shadowing sign" and hypertelorism could help to improve the accuracy of prenatal ultrasound diagnosis for Apert syndrome and effectively reduce missed and misdiagnosis.

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.