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

Inflammatory diseases (IDs) are a general term of diseases characterized by chronic inflammation as the primary pathogenetic mechanism, which seriously affect the quality of patient′s life and cause significant social and medical burden. Current drugs for IDs include nonsteroidal anti-inflammatory drugs, corticosteroids, immunomodulators, biologics, and antioxidants, but these drugs may cause gastrointestinal side effects, induce or worsen infections, and cause non-response or intolerance. Given the outstanding performance of metal polyphenol network (MPN) in the fields of drug delivery, biomedical imaging, and catalytic therapy, its application in the diagnosis and treatment of IDs has attracted much attention and significant progress has been made. In this paper, we first provide an overview of the types of IDs and their generating mechanisms, then sort out and summarize the different forms of MPN in recent years, and finally discuss in detail the characteristics of MPN and their latest research progress in the diagnosis and treatment of IDs. This research may provide useful references for scientific research and clinical practice in the related fields.

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 the effects of saphenous nerve combined with posterior capsular block of knee joint on stress response,analgesic effect and joint function recovery of patients after total knee arthroplasty.Methods A total of 98 patients who received total knee arthroplasty in our hospital from January 2021 to January 2022 were selected and divided into the observation group(received saphenous nerve combined with posterior capsular block of knee joint)and the control group(received saphenous nerve block)by random number table,with 49 patients in each group.The visual analogue scale(VAS)score of resting and dynamic pain 6 hours,12 hours and 24 hours after surgery of patients in the two groups were compared.The range of knee joint motion before surgery,3 days,5 days and 7 days after surgery of patients in the two groups were compared.The stress indexes[cortisol(Cor),adrenocorticotropic hormone(ACTH)],and pain mediator indexs[calcitonin gene-related peptide(CGRP),beta-endorphins(β-EP),6-keto prostaglandin E1α(6-Keto-pGE1α),substance P(SP)]before surgery,4 hours,12 hours,24 hours,and 48 hours after surgery of patients in the two groups were compared.The occurrence of adverse reactions during treatment of patients in the two groups were recorded.Results There were statistically significant differences in the resting and dynamic VAS scores at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There were statistically significant differences in the range of knee joint motion at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There were statistically significant differences in the Cor and ACTH contents at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There were statistically significant differences in the contents of β-EP,SP,CGRP and 6-keto-PGE1α at different time points of patients in the two groups in terms of time factors,inter-group factors and interaction factors(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion Saphenous nerve combined with posterior capsular block of knee joint for total knee arthroplasty can reduce patients' stress response,enhance postoperative analgesic effect,and improve the early motor function,with high safety.

Objective:To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia(CLL).Methods:The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively.Results:The median age of 59 CLL patients was 60.5(36-78).After one year of BTKi treatment,the CLL clones(CD5+/CD19+)of 51 cases(86.4％)were significantly reduced,in which the number of cloned-B cells decreased significantly from(46±6.1)× 109/L to(2.3±0.4)× 109/L(P=0.0013).But there was no significant change in the number of non-cloned B cells(CD19+minus CD5+/CD19+).After BTKi treatment,IgA increased significantly from(0.75±0.09)g/L to(1.31±0.1)g/L(P＜0.001),while IgG and IgM decreased from(8.1±0.2)g/L and(0.52±0.6)g/L to(7.1±0.1)g/L and(0.47±0.1)g/L,respectively(P＜0.001,P=0.002).BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients,which manifested as both a decrease in total number of T cells from(2.1±0.1)× 109/L to(1.6±0.4)× 109/L and NK/T cells from(0.11±0.1)× 109/L to(0.07±0.01)× 109/L(P=0.042,P=0.038),both an increase in number of CD4+cells from(0.15±6.1)× 109/L to(0.19±0.4)× 109/L and CD8+cells from(0.27±0.01)× 109/L to(0.41±0.08)× 109/L(both P＜0.001).BTKi treatment also up-regulated the expression of interleukin(IL)-2 while down-regulated IL-4 and interferon(IFN)-γ.However,the expression of IL-6,IL-10,and tumor necrosis factor(TNF)-α did not change significantly.BTKi treatment could also restored the diversity of TCR and BCR in CLL patients,especially obviously in those patients with complete remission(CR)than those with partial remission(PR).Before and after BTKi treatment,Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001(P＜0.001),while in patients with PR was 0.01±0.03 and 0.05±0.02(P＞0.05),respectively.Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15(P＜0.001),while in patients with PR was 0.15±0.009 and 0.23±0.18(P＜0.05),respectively.Conclusions:BTKi treatment can shrink the clone size in CLL patients,promote the expression of IgA,increase the number of functional T cells,and regulate the secretion of cytokines such as IL-2,IL-4,and IFN-γ.BTKi also promote the recovery of diversity of TCR and BCR.BTKi treatment contributes to the reconstitution of immune function in CLL patients.

Objective:To investigate the prevalence of enterovirus 71 (EV71) and the genetic characteristics of VP1 region in common hand, foot and mouth disease (HFMD) cases in Shenzhen from 2016 to 2022.Methods:Throat swabs from mild HFMD in Shenzhen sentinel hospitals were collected from 2016 to 2022. A total of 38 EV71-positive samples were screened from these throat swabs and were sequenced. Then, the VP1 sequence of these EV71-positive samples were analyzed for their phylogenetic evolution by bioimformatics software DNAStar and MEGA 6.Results:From 2016 to 2022, the number of EV71 infections among HFMD patients in Shenzhen sentinel hospitals decreased from 136 in 2016 to 0 in 2022. The mumber of EV71 infections in 2018 and 2019 decreased by 96.3%(257/267) compared to that in 2016 and 2017. From 2020 to 2022, the number of EV71 infections decreased to 0. During this period, the EV71 vaccination rate among HFMD patients increased from 6.4% to 39.6%; Evolutionary analysis showed that the nucleotide homology and amino acid homology between 38 EV71 sample strains in Shenzhen from 2016 to 2022 were 91.8%-99.9% and 98.3%-100.0%, all belonging to the C4a subgenotype; Among them, 26 strains wene local epidemic strains, and 11 strains were imported from other provinces, with a close genetic relationship with epidemic strains in Hainan, Yunnan, Sichuan, Tianjin, Henan, Jilin, and other places. One strain from 2017 had the closest genetic relationship with the US epidemic strain OP207969-USA-2017. Further comparing the EV71 epidemic strains in Shenzhen from 2016 to 2022 and EV71 severe strains, it was found that the EV71 strains in Shenzhen carried four amino acid mutation sites related to severe condition, named R22H, K43R, I249V and T289A.Conclusions:The EV71 epidemic strains in Shenzhen from 2016 to 2022 all belong to the C4a subgenotype, and the number of EV71 infection shows a downward trend with the increase of vaccine coverage rate. At the same time, the distribution of EV71 virus strains in Shenzhen shows a significant decrease in local strains and a predominance of imported strains. There are a total of four amino acid mutation sites associated with severe cases in the EV71 sample strains in Shenzhen from 2016 to 2022. Among them, 22R and 289T are located at the N and C ends of VP1, which are related to EV71 adsorption and targeting cells. The 43R site is associated with binding ability to Annexin2 protein, which enhances cell binding ability.

Objective To propose an evaluation and screening indicator for the reliability of emergency ventilators.Methods Firstly,a regression model was used to clean the data and remove noise to ensure the accuracy of regression analysis.Then,four groups of highly correlated data combinations,including inspiratory tidal volume-minute expiratory volume,peak airway pressure-minute expiratory volume,peak airway pressure-inspiratory tidal volume and positive end-expiratory pressure(PEEP)-mean airway pressure,were determined with the methods of curve fitting and transfer function,and the difference between the theoretical output and the actual output of the data combinations was regarded as an indicator to judge whether the ventilator functioned well or not;finally,the indicator proposed was applied to single and multiple ventilators,and the feasibility of the indicator was determined by the proportion of the ventilators functioning well.Results The evaluation results with a single ventilator showed the four groups of data combinations had the actual output fitted well with the theoretical output,and all the differences between the theoretical output and the actual output were lower than the threshold;the results with multiple ventilators indicated there were 71.49％ventilators functioning well,which was very close to the actual result that 72％ventilators behaved well.Conclusion The evaluation and screening indicator for emergency ventilators has high feasibility,and theoretical support is provided for reliability assessment and selection of series of emergency treatment equipment.[Chinese Medical Equipment Journal,2024,45(7):8-16]

Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

Tumor cells use glycolysis to provide material and energy under hypoxic conditions to meet the energy requirements for rapid growth and proliferation， namely the Warburg effect. Even under aerobic conditions， tumor cells mainly rely on glycolysis to provide energy. Therefore， glucose transporter protein 1（GLUT1）， which is involved in the process of glucose metabolism， plays an important role in tumorigenesis， development and drug resistance， and is considered to be one of the important targets in the treatment of malignant tumors. In recent years， research on tumor glucose metabolism has gradually become a hot spot. It has been shown that various factors are involved in the regulation of tumor energy metabolism， among which the role of GLUT1 is the most critical. In this paper， the authors reviewed the latest research progress of GLUT1-targeted traditional Chinese medicine（TCM） active ingredient nano-delivery system in tumor therapy， aiming to reveal the feasibility and effectiveness of this system in the delivery of chemotherapeutic drugs. The GLUT1-targeted TCM active ingredient nano-delivery system can overcome the bottleneck of the traditional targeting strategy as well as the high-permeability long retention（EPR） effect. In summary， the authors believe that the GLUT1-targeted TCM active ingredient nano-delivery system provides a new strategy for targeted treatment of tumors and has a broad application prospect in tumor prevention and treatment.

ObjectiveTo investigate the role and possible mechanism of action of rhubarb decoction （RD） retention enema in improving inflammatory damage of brain tissue in a rat model of mild hepatic encephalopathy （MHE）. MethodsA total of 60 male Sprague-Dawley rats were divided into blank group （CON group with 6 rats） and chronic liver cirrhosis modeling group with 54 rats using the complete randomization method. After 12 weeks， 40 rats with successful modeling which were confirmed to meet the requirements for MHE model by the Morris water maze test were randomly divided into model group （MOD group）， lactulose group （LT group）， low-dose RD group （RD1 group）， middle-dose RD group （RD2 group）， and high-dose RD group （RD3 group）， with 8 rats in each group. The rats in the CON group and the MOD group were given retention enema with 2 mL of normal saline once a day； the rats in the LT group were given retention enema with 2 mL of lactulose at a dose of 22.5% once a day； the rats in the RD1， RD2， and RD3 groups were given retention enema with 2 mL RD at a dose of 2.5， 5.0， and 7.5 g/kg， respectively， once a day. After 10 days of treatment， the Morris water maze test was performed to analyze the spatial learning and memory abilities of rats. The rats were analyzed from the following aspects： behavioral status； the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） and the level of blood ammonia； pathological changes of liver tissue and brain tissue； the mRNA and protein expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （AKT）， and mammalian target of rapamycin （mTOR） in brain tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the MOD group， the RD1， RD2， and RD3 groups had a significantly shorter escape latency （all P<0.01）， significant reductions in the levels of ALT， AST， IL-1β， IL-6， TNF-α， and blood ammonia （all P<0.05）， significant alleviation of the degeneration， necrosis， and inflammation of hepatocytes and brain cells， and significant reductions in the mRNA and protein expression levels of PI3K， AKT， and mTOR in brain tissue （all P<0.05）， and the RD3 group had a better treatment outcome than the RD1 and RD2 groups. ConclusionRetention enema with RD can improve cognitive function and inflammatory damage of brain tissue in MHE rats， possibly by regulating the PI3K/AKT/mTOR signaling pathway.