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.

This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL^-1) were used to induce fibrotic model, and high glucose (30 mmol·L^-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.

Objective To explore the efficacy and safety of ticagrelor de-escalation and nicorandil therapy in elderly patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods A total of 300 elderly patients with ACS were selected from the Sixth and Seventh Medical Center of Chinese PLA General Hospital and Beijing Chaoyang Integrative Medicine Emergency Rescue and First Aid Hospital from November 2016 to June 2019,including 153 males and 147 females,aged>65 years old.All the patients received PCI,and all had double antiplatelet therapy(DAPT)scores≥2 and a new DAPT(PRECISE-DAPT)score of≥25.All patients were divided into two groups by random number table method before operation:ticagrelor group(n=146,ticagrelor 180 mg load dose followed by PCI,and ticagrelor 90 mg bid after surgery)and ticagrelor de-escalation + nicorandil group(n=154,ticagrelor 180 mg load dose followed by PCI,ticagrelor 90 mg bid+nicorandil 5 mg tid after surgery,changed to ticagrelor 60 mg bid+ nicorandil 5 mg tid 6 months later).Follow-up was 12 months.The composite end points of cardiovascular death,myocardial infarction and stroke,the composite end points of mild hemorrhage,minor hemorrhage,other major hemorrhage and major fatal/life-threatening hemorrhage as defined by the PLATO study,and the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding within 12 months in the two groups were observed.Results The comparison of general baseline data between the two groups showed no statistically significant difference(P>0.05).There was also no significant difference in the composite end points of cardiovascular death,myocardial infarction and stroke between the two groups(P>0.05).The cumulative incidence of bleeding events in ticagrelor de-escalation + nicorandil group was significantly lower than that in ticagrelor group(P<0.05),while the composite end points of cardiovascular death,myocardial infarction,stroke and bleeding were also significantly lower than those in tecagrelor group(P<0.05).Conclusion In elderly patients with ACS,the treatment of ticagrelor de-escalation + nicorandil after PCI may not increase the incidence of ischemic events such as cardiovascular death,myocardial infarction or stroke,and it may reduce the incidence of hemorrhagic events.

Objective:To investigate the expression of retinoic acid receptor responsive gene 2 (RARRES2), microtubule microfilament cross-linking factor 1 (MACF1), and core protein polysaccharide (DCN) in cerebrospinal fluid (CSF) of patients with neurosyphilis, and their diagnostic value for neurosyphilis.Methods:A total of 64 non neurosyphilis syphilis patients (syphilis group) and 78 neurosyphilis patients (neurosyphilis group) admitted to the Second Hospital of Nanjing between June 2020 and September 2022 were included. Among neurosyphilis patients, there were 48 early neurosyphilis patients (early group) and 30 late neurosyphilis patients (late group). Patients with neurosyphilis are treated with routine symptomatic therapy and antibiotic therapy to expel syphilis. The mRNA levels of RARRES2, MACF1, and DCN in CSF of patients with neurosyphilis before and after treatment were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the neurological function of patients with neurosyphilis before and after treatment. The diagnostic value of various indicators for neurosyphilis was analyzed using receiver operating characteristic (ROC) curves.Results:The mRNA levels of RARRES2, MACF1, and DCN in CSF of patients with neurosyphilis were higher than those in the syphilis group (all P<0.001). The mRNA levels of RARRES2, MACF1, and DCN in the CSF of patients with advanced neurosyphilis were higher than those in the early group (all P<0.001). Compared with before treatment, the NIHSS score and RARRES2, MACF1, and DCN mRNA levels of neurosyphilis patients decreased after treatment (all P<0.001). The area under the curve (AUC), sensitivity, and specificity of the combined diagnosis of RARRES2, MACF1, and DCN mRNA in CSF for neurosyphilis were 0.995%, 100.00%, and 93.75%, respectively. The AUC and sensitivity were higher than those of individual diagnosis. Conclusions:The expression of RARRES2, MACF1, and DCN is elevated in CSF of patients with neurosyphilis, and is associated with disease severity and treatment response. These three genes may be candidate biomarkers for diagnosing neurosyphilis.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To analyze the relationship between inflammatory burden index (IBI) and the diagnosis and prognosis of gastric cancer.Methods:A total of 180 patients with gastric cancer admitted to the First Affiliated Hospital of Xi'an Medical University from January 1, 2017 to December 31, 2021 were selected as the gastric cancer group, 180 cases of gastric precancerous diseases treated in this hospital during the same period were selected as the precancerous disease group, 180 healthy individuals who underwent physical examinations in this hospital during the same period were selected as the control group. The value of IBI in the diagnosis of gastric cancer was analyzed. The IBI values of the three groups were compared by one-way analysis of variance, and the optimal cut-off values of different indicators were determined by receiver operator characteristic (ROC) curve to further evaluate the diagnostic value of IBI for gastric cancer. LASSO regression analysis was performed using the R software package glmnet to screen variables. Univariate and multivariate Cox regression analysis were performed on the screened variables to further determine the independent risk factors affecting the prognosis of patients with gastric cancer.Results:The levels of IBI in gastric cancer, precancerous disease, and control group were 46.69±8.38, 35.53±6.11, and 21.47±4.36, respectively, with a statistically significant difference ( F=681.45, P<0.001). Further pairwise comparisons showed that the gastric cancer group was higher than the precancerous disease group and the control group, and the precancerous disease group was higher than the control group, with statistically significant differences ( t=14.43, P<0.001; t=34.15, P<0.001; t=25.13, P<0.001). ROC curve analysis showed that the optimal cut-off value for the neutrophil to lymphocyte ratio (NLR) was 3.15 (AUC=0.65, 95% CI: 0.54-0.73), with a specificity of 92.31% and a sensitivity of 43.97%. The optimal cut-off value for the platelet to lymphocyte ratio (PLR) was 137.36 (AUC=0.59, 95% CI: 0.51-0.68), with a specificity of 93.66% and a sensitivity of 34.98%. The optimal cut-off value for lymphocyte to monocyte ratio (LMR) was 5.18 (AUC=0.69, 95% CI: 0.58-0.76), with a specificity of 61.29% and a sensitivity of 73.33%. The optimal cut-off value for panimmune inflammation value (PIV) was 276.57 (AUC=0.73, 95% CI: 0.65-0.78), with a specificity of 78.41% and a sensitivity of 59.77%. The optimal cut-off value for the systemic immune inflammatory index (SII) was 654.37 (AUC=0.73, 95% CI: 0.66-0.78), with a specificity of 86.32% and a sensitivity of 62.11%. The optimal cut-off value for the IBI was 49.12 (AUC=0.82, 95% CI: 0.79-0.92), with a specificity of 85.36% and a sensitivity of 65.82%. LASSO regression analysis showed that there were 8 prognostic variables related to survival, including IBI, T stage, N stage, age, carcinoembryonic antigen (CEA), SII, PIV, and tumor grade. The results of univariate analysis showed that IBI ( HR=4.57, 95% CI: 3.82-5.32, P<0.001), T stage ( HR=2.54, 95% CI: 1.75-3.31, P<0.001), N stage ( HR=1.69, 95% CI: 1.15-2.21, P=0.032), CEA ( HR=1.38, 95% CI: 1.06-1.75, P=0.032), and tumor grade ( HR=1.87, 95% CI: 1.34-2.59, P=0.026) were prognostic factors for gastric cancer patients. The results of multivariate analysis showed that IBI ( HR=3.96, 95% CI: 3.51-4.48, P<0.001), T stage ( HR=2.31, 95% CI: 1.63-3.02, P=0.023), tumor grade ( HR=1.49, 95% CI: 1.12-1.83, P=0.042) were independent risk factors affecting the prognosis of gastric cancer patients. Compared with low-level IBI gastric cancer patients, the risk of death in high-level IBI patients was up to 3.96 times. Conclusion:IBI may be an important marker for diagnosis and prognosis prediction of gastric cancer, which has certain scientific and clinical value in the diagnosis and treatment of gastric cancer.

Objective:To explore the value of mitoxantrone hydrochloride injection for tracing in endoscopic thyroidectomy (ETE) via anterior chest approach for papillary thyroid carcinoma (PTC) .Methods:A retrospective analysis was conducted on patients undergoing ETE via anterior chest approach for PTC admitted to Beijing Longfu Hospital (Medical Treatment Combination with Peking Union Medical College Hospital) from Sep. 2022 to Mar. 2024. The patients were divided into two groups: the control group (without tracer) and the tracer group (with mitoxantrone hydrochloride injection for tracing). All surgeries were performed by the same thyroid surgical team. Baseline, postoperative pathologies and complications were compared between the 2 groups.Results:A total of 25 patients (13 in the control group and 12 in the tracer group) were included in this study, and the average dissection of unilateral central region lymph nodes in the tracer group was 7.4±4.6, significantly more than in the control group (2.4±1.9) ( P=0.004). There were no instances of mistakenly resected parathyroid gland in the postoperative pathology or accidental injury of recurrent laryngeal nerve in either group. The incidence of transient hypocalcemia did not significantly different between the two groups ( P=0.503). However, the incidence of transient hypoparathyroidism in the tracer group was 1 (1/12,8.3%), significantly lower than in the control group 4 (4/13,30.8%) ( P=0.009). The tracer group exhibited more impressive levels in parathyroid hormone (5.4±8.1) pg/mL compared to the control group (20.0±11.1) pg/mL ( P=0.001) .The total volume of postoperative drainage in the tracer group (142.9±71.7) mL was more than that of the control group (87.7±38.8) mL ( P=0.030). But It did not affect the extubation time in either group ( P=0.610). No residual tracer was observed at the skin puncture site in the tracer group after 2 weeks. Conclusions:Mitoxantrone hydrochloride injection for tracing as tracer in ETE via breast approach can increase the number of pathological lymph nodes dissection in cervical central region. Combined with negative development, identifying and protecting the function of parathyroid glands show feasible and potential application value to improve the safety of thyroidectomy. The use of mitoxantrone hydrochloride injection for tracer has the risk of increased exudation from the surgical area, but does not affect the time to remove the drain.

Objective:To explore the use of near-infrared autofluorescence probe (NIRAF-P) and its application in identifying parathyroid glands during surgery.Methods:A total of 68 patients undergoing thyroid surgery at Peking Union Medical College Hospital and Beijing Longfu Hospital between Dec. 2023 and Jun. 2024 were selected. During the operation, the near-infrared parathyroid gland detector was used to identify the parathyroid gland tissue to be tested, and histopathological examination was performed. The positive predictive value and accuracy of the near-infrared parathyroid gland detector were analyzed.Results:A total of 111 parathyroid glands were identified in 68 patients, and the positive predictive value and accuracy of the NIRAF-P were 95.5% and 94.6%, respectively.Conclusions:The NIRAF-P has high accuracy in identifying parathyroid glands. The standardized application of the NIRAF-P can help improve the efficiency of identifying parathyroid glands during surgery.

Human physiological indicators have become an important standard for assessing health in modern society.Traditional detection methods often require a separate laboratory,complex operation process and long detection time,so it is urgent to develop portable,fast and accurate on-site detection technologies for bioanalysis.Point-of-care testing(POCT),which differs from traditional laboratory testing,can realize the rapid in situ detection of biomarkers without the complicated analytical process of the laboratory.Smartphones,which are an essential tool in our daily life,not only have independent operating systems and built-in storage functions,but also have high-definition cameras,which have great application potential in POCT visualization.The combination of various biosensing technologies and smartphones has developed into a new direction in the field of POCT.This review mainly introduced the research progress of smartphone-based visual biosensors in POCT in recent years,including colorimetric sensors,fluorescence sensors,chemiluminescence sensors and electrochemiluminescence sensors.Finally,the problems faced by smart-phone-based visual biosensors in the application of POCT were summarized,and their future development was prospected.

Objective:The clinical data of prenatal stillbirth were analyzed in order to increase the understand-ing of the causes of stillbirth.Methods:Prenatal stillbirth cases that terminated pregnancy in Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University from January 2018 to December 2022 were col-lected,and the distribution characteristics of clinical data and the stillbirth causes were analyzed.The causes of death were classified according to the standards developed by the Stillbirth Collaborative Research Network(SCRN)in the United States,and they were divided into clear cause-of-death group and unknown cause-of-death group.The different characteristics of the two groups were compared and analyzed.Results:There were 210 ca-ses of prenatal stillbirth during the study period,and 104 cases met the inclusion criteria.Among them,33 cases(31.7%)had autopsy results,39 cases(37.5%)had genetic results,and 75 cases(72.1%)had placental pathol-ogy.According to the classification of SCRN standard,55 cases(52.9%)were probably related to the cause of death,33 cases(31.7%)were classified as possible,13 cases(12.5%)were probably unrelated,and 3 cases(2.9%)could not be attributed to the cause of death,that is,84.6%(88 cases)in the clear cause of death group and 15.4%(16 cases)in the unknown cause of death group.The rate of placental pathological examination in the clear cause of death group was significantly higher than that in the unknown cause of death group(78.4%).In the classification of causes of death,placental pathological changes accounted for the largest proportion,account-ing for 26.9%(28 cases),followed by pregnancy complications accounting for 25.0%(26 cases),and 15.4%of the cases were still unexplained.Conclusions:Placental pathology is of great significance for clarifying the cause of stillbirth.It is feasible to use SCRN to classify the etiology of stillbirth.Pathological placental conditions account for a relatively high proportion in the classification of stillbirth causes.It is recommended that each case of stillbirth placenta should undergo pathological examination.