Oral lichen planus (OLP) is a chronic inflammatory disease occurring in the oral mucosa. Clinically, OLP presents with various lesion morphologies, attributed to differences in host immune responses. T-helper 17 cells (Th17) are a crucial component of the cellular immune response, primarily functioning through the secretion of interleukin 17 (IL-17). IL-17 plays a dual role in the oral mucosa: on one hand, it exerts a protective effect by promoting the recruitment of neutrophils driven by chemokines, enhancing the secretion of antimicrobial peptides, and strengthening the mucosal barrier; on the other hand, it binds to target cells in the mucosal tissue, activating downstream inflammatory signaling pathways such as nuclear factor kappa-B(NF-κB) and mitogen-activated protein kinase(MAPK), thereby initiating a pro-inflammatory cascade. This process increases the secretion of pro-inflammatory factors and promotes the recruitment and activation of immune cells, exacerbating inflammation. Current research extensively explores the correlation between the Th17/IL-17 axis and the pathogenesis and progression of OLP. This paper aims to review these developments to provide a research foundation for further elucidating the immunological mechanisms of OLP. Literature review results indicate that upregulation of Th17 and IL-17 in local lesion tissues and peripheral blood of OLP patients may be a key molecular event in the development of OLP. Compared to non-erosive OLP, higher expression levels of Th17 and IL-17 in the tissues and blood of patients with erosive OLP suggest a positive correlation between Th17/IL-17 and disease severity. Clinical studies demonstrate that targeted drugs against the Th17/IL-17 axis, by directly blocking IL-17 or inhibiting the production of Th17 cells, can effectively improve mucosal damage in OLP patients, showcasing potential as a new target for immune therapy. However, whether Th17 and IL-17 influence the pathogenesis of OLP by regulating the oral microbiome remains unclear. In summary, the Th17/IL-17 axis holds potential value as a new target for the immune therapy of OLP, warranting further in-depth research into its biological functions and signaling mechanisms within the inflammatory process of OLP.

ObjectiveTo investigate the regulatory effect and potential mechanisms of isocitrate dehydrogenase 3A （IDH3A） on cardiomyocyte hypertrophy. MethodsThe expression of IDH3A in the myocardium of healthy volunteers （n=10） and patients with heart failure （HF） （n=10）， and in the myocardium of mice subjected to transverse aortic constriction （TAC） surgery and sham operation， as well as in phenylephrine （PE）-induced neonatal rat ventricular cardiomyocytes （NRVCs）， was assessed by real-time quantitative polymerase chain reaction （RT-qPCR） and Western blot assay. The effect of adenovirus-mediated overexpression of IDH3A on the expression of hypertrophy-related genes in PE-induced NRVCs was also evaluated. The effect of IDH3A on NRVCs area was examined by phalloidin staining assay. A mutant of IDH3A with abolished enzymatic activity， IDH3A_D208A， was generated through site-directed mutagenesis. The impact of this IDH3A mutant on the hypertrophic phenotype， ATP and ROS levels in NRVCs was evaluated to investigate whether the regulatory role of IDH3A in cardiomyocyte hypertrophy was dependent on its enzymatic activity. The effect of exogenous α-ketoglutaric acid （AKG） on cardiomyocyte hypertrophy was also detected by Western blot and phalloidin staining assay， respectively. ResultsIDH3A was significantly decreased in the myocardium of HF patients， in the myocardium of TAC-operated mice， and in PE-induced NRVCs （P = 0.005 2，P = 0.026 6，P = 0.041 3 and P = 0.006 6， respectively）. Overexpression of IDH3A markedly suppressed the expression of hypertrophy-related genes and the increase of cell size of PE-induced NRVCs （P < 0.000 1， P = 0.000 1 and P = 0.000 2， respectively）. The ATP and ROS analysis indicated that IDH3A inhibited the increases of ATP and ROS levels in PE-induced NRVCs （P = 0.001 2 and P<0.000 1， respectively）， whereas the enzymatically inactive IDH3A mutant lacked this effect. Exogenous AKG provision could， but overexpression of IDH3A mutant failed to suppress PE-induced NRVCs hypertrophy. ConclusionIDH3A inhibits cardiomyocyte hypertrophy via elevating AKG level， providing scientific evidence for study on IDH3A-based treatment of cardiac hypertrophy.

OBJECTIVE To establish HPLC methods with different separation principles to analyze the relevant impurities in the APIs of bivalirudin from seven enterprises, to provide a basis for the comprehensive control of related substances of bivalirudin. METHODS Reversed-phase high performance liquid chromatography(RP-HPLC) was used to separate and analyze 11 kinds of impurities. Hydrophilic chromatography(HILIC)-HPLC was used to control four process impurities. Polymers were determined by size exclusion chromatography(SEC)-HPLC. RESULTS The established RP-HPLC could effectively separate the principal component and 11 impurities, the correction factors of 11 impurities were between 0.8−1.2, the detection concentration of bivalirudin was 0.1 μg·mL−1, and the detection limit was 0.004%. The established HILIC-HPLC could effectively separate the principal components and four process impurities, and the detection concentration of bivalirudin was 0.3 μg·mL−1, and the detection limit was 0.01%. Under SEC-HPLC conditions, the polymer and bivalirudin peaked sequentially, the resolution of the two was 2.9, the detection concentration of bivalirudin was 6 ng·mL−1, and the detection limit was 0.000 6%. Fifteen kinds of known impurities and polymers in 15 batches of samples from 7 enterprises were calculated by the self-control method of principal components, and the impurity contents from different enterprises had a certain correlation with their production processes. CONCLUSION The three different principles of the method have good specificity, high sensitivity, good durability, and reliable results, and can be used for quality control of substances related to bivalirudin.

BACKGROUND:Currently,electrospun nanofibers,which are biomimetic materials of natural extracellular matrix and contain a three-dimensional network of interconnected pores,have been successfully used as scaffolds for various tissue regeneration,but are still faced with the challenge of extending the biomaterials into three-dimensional structures to reproduce the physiological,chemical as well as mechanical properties of the tissue microenvironment. OBJECTIVE:To summarize the process and principles of electrostatic spinning and to explore the applications of the resulting electrospun nanofibers in tissue regeneration of skin,blood vessels,nerves,bone,cartilage and tendons/ligaments. METHODS:With"electrospinning,electrospun nanofibers,electrospun nanofiber scaffolds,tissue regeneration"as the Chinese and English search terms,Google Academic Database,PubMed,and CNKI were searched,and finally 88 articles were included for review. RESULTS AND CONCLUSION:(1)The electrospun nanofibers are a natural fibrous extracellular matrix mimetic material and contain a three-dimensional network of interconnected pores that have been successfully used as scaffolds for a variety of tissue regeneration applications.(2)Several papers have described the great potential of electrospun nanofiber scaffolds applied to the regeneration of skin,blood vessels,nerves,bones,cartilage and tendons/ligaments,providing a solid theoretical basis for its final application in clinical disease treatment,or for its transformation into practical products to enter the market.(3)However,the current research results are mostly based on cell experimental research results in vitro,and whether it can be finally applied to human body still needs clinical verification.(4)At present,many kinds of electrospun products for various clinical needs have been commercialized in and outside China,indicating that the research field of electrospun nanofiber scaffolds for soft and hard tissue regeneration has great research value and application potential.

Objective To investigate the common symptoms and associated disease characteristics of hyperhomocysteinemia in cere-bral infarction patients and the correlation analysis of influencing factors.Methods A total of 151 participants with blood homocysteine≥15μmol/L and 86 participants with blood homocysteine＜15μmol/L were identified as the hyperhomocysteinemia with cerebral infarction group(H group)and the normal cerebral infarction group(N group),respectively.The symptoms and influence factors in the two groups were compared.Results Among cerebral infarction patients,patients in H group were older(P=0.049),more male(P=0.002),had a history of smoking(P=0.025),diabetes(P=0.008),hyperlipidemia(P=0.034),folate deficiency(P=0.002)and associated cognitive impairment(P=0.009)and language barrier(P=0.043).Binary Logistic regression analysis showed that age(P=0.023),diabetes(P=0.018),folate deficiency(P=0.026),and cognitive impairment(P=0.019)were independent related factors of in-creased blood homocysteine level.Conclusion Cerebral infarction patients with hyperhomocysteinemia are elderly,and most of them have diabetes,folate deficiency,and cognitive impairment.

Objective:To investigate the efficacy of an extracorporeal diaphragm pacemaker (EDP) combined with airway clearance technology (ACT) in the treatment of pulmonary infection in older adult patients with dementia and its impact on diaphragmatic mobility and thickness.Methods:A total of 60 patients with dementia and pulmonary infections who received treatment at The Second Hospital of Jinhua from June 2022 to February 2023 were included in this prospective study. These patients were randomly divided into an observation group and a control group, with 30 patients in each group. The control group received ACT treatment, while the observation group received EDP treatment on the basis of ACT treatment. Two groups were treated for 4 successive weeks. Efficacy was compared between the two groups. Before and after treatment, sputum color score, sputum quality score, diaphragmatic mobility, and diaphragmatic thickness were compared between the two groups.Results:The overall response rate in the observation group was 93.33% (28/30), which was significantly higher than 73.33% (22/30) in the control group ( Z = 2.08, P = 0.038). After treatment, the sputum color score, sputum quality score, and sputum volume in the observation group were (0.46 ± 0.12) points, (0.34 ± 0.10) points, and (8.47 ± 1.23) mL, respectively, which were significantly lower than (0.89 ± 0.17) points, (0.76 ± 0.18) points, and (13.25 ± 2.87) mL, respectively, in the control group ( t = 11.32, 11.17, 8.38, all P < 0.001). After treatment, the diaphragmatic mobility and thickness in the observation group were (13.52 ± 0.51) mm and (0.52 ± 0.06) mm, respectively, which were significantly greater than (12.76 ± 0.41) mm and (0.44 ± 0.04) mm, respectively, in the control group ( t = -6.36, -6.08, both P < 0.001). Conclusion:The combined application of EDP and ACT shows a significant therapeutic effect on patients with dementia and pulmonary infection, effectively improving their pulmonary function, increasing the mobility and thickness of the diaphragm, and alleviating difficulties in breathing.

Objective To overcome the limitations of existing human respiratory syncytial virus(hRSV)animal models,such as semi-permissiveness and short duration of infection,this study established an IL2rg gene knockout(IL2rg-/-)rat model using TALEN gene editing technology.Methods The animal model was infected with hRSV intranasally.Clinical characteristics,body weight,and temperature changes were observed over the infection period(0～35 days).The total viral loads in respiratory organs,such as the nasal tissue,trachea,and lungs,were measured at various time points(4,11,20,and 35 days post-infection).Pathological analysis was conducted on target organs at the endpoint of observation(35 days post-infection).Changes in peripheral blood T,B,NK,and NKT cells and various cytokines were assessed at various time points(4,20,and 35 days post-infection).Results(1)IL2rg/-knockout rats sustained high viral loads in the nasal cavity upon intranasal inoculation with hRSV.The average peak titer rapidly reached 1 × 1010 copies/g in nasal tissue and 1 × 107 copies/g up to 5 weeks post-infection.(2)However,no significant pathological changes were noted in nasal,tracheal,or lung tissues.(3)An increase was observed in the content of peripheral blood B cells in hRSV-infected IL2rg--rats.(4)IL-6 and MCP-1 were increased in the early stage of infection and then decreased at the end of the observation period.Conclusions This study established a new IL2rg-/-rat model using TALEN technology and found that this model effectively supported high-level replication and long-term infection of hRSV,providing a good basis for antiviral drug screening and in vivo efficacy evaluation of anti-hRSV antibodies.

Objective Through a multi-software visual analysis of the literature on the influence of T cells on rheumatoid arthritis(RA)in recent ten years,the research hotspot and frontier development in this field were summarized.Methods The Chinese and English literature on the influence of T cells on RA from 2012 to 2022 years was retrieved from CNKI and Web of Science database as the research object.CiteSpace and VOSviewer software were used to analyze the number of publications,authors and keywords.Results 519 articles in Chinese and 861 in English were retrieved.The results showed that the number of articles in Chinese increased slowly from 2020 to 2022 years,while the overall trend in English was stable.Keyword analysis shows that it is predicted that future research in this field will focus on the pathogenesis of T cells in RA,the mechanism of bone destruction in RA,disease activity,oxidative stress.Conclusion The influence of T cells on RA has attracted much attention in the past,present and future,and has great research value.However,due to the differences in research priorities at home and abroad,the teams should interact positively and communicate with each other to reveal the internal mechanism of RA and provide theoretical basis for targeted therapy.

Objective:To discuss the biological function of the spacer domain of ADAM metalloproteinase with thrombospondin type 1 motifs 13(ADAMTS13)in the cleaving process of von Willebrand factor(vWF),and to clarify the role of ADAMTS13 in the pathogenesis of thrombotic thrombocytopenic purpura(TTP).Methods:The point mutation method was introduced sequentially into the amino acid residues TEDRLPR of the ADAMTS13 spacer domain(mutants M1-M7)by site-directed mutagenesis.The constructed ADAMTS13 and its mutants plasmids were transfected into the human embryonic kidney HEK293 cells,and the recombinant proteins were purified after stable expression.The cleavage capabilities of both wild type and mutant ADAMTS13 were observed under denaturation conditions,shear stress,and after treatment with ADAMTS13 antibodies.Results:The fluorescence resonance energy transfer(FRET)assay results showed that compared with wild type ADAMTS13,the cleavage abilities of ADAMTS13 mutant M4(R635A)and mutant M7(R638A)on the FRET-vWF73 were decreased(P＜0.05).Under denaturation conditions,the wild-type ADAMTS13 could cleave the vWF multimers;compared with wild-type ADAMTS13,the cleavage activities of ADAMTS13 mutant M4(R635A)and mutant M7(R638A)were significantly decreased(P＜0.01).Under in vitro shear stress,compared with wild type ADAMTS13,the abilities of ADAMTS13 mutant M4(R635A)and mutant M7(R638A)to cleave vWF multimers were significantly decreased(P＜0.01).Compared with wild type ADAMTS13,the binding affinity between vWF and ADAMTS13 mutant M4(R635A)and mutant M7(R638A)had no significant difference(P＞0.05),indicating there were multiple binding sites between C-terminal of ADAMTS13 and vWF.The ADAMTS13 antibodies were able to inhibit the cleavage ability of both wild-type and mutant ADAMTS13 to some extent.Conclusion:The activity of ADAMTS13 after spacer domain mutation is decreased.The ADAMTS13 mutant M4(R635A)and mutant M7(R638A)may be the important action sites for AD AMTS 13 in substrate recognition.

Objective To investigate whether VHD prefabricated foot orthoses can reduce the incidence of lower limb overuse injury (LLOI) in naval recruits. Methods Totally 400 recruits who underwent enlistment training were enrolled and randomly assigned to the intervention group (n=200) and control group (n=200). During the enlistment training,the recruits in the intervention group wore VHD prefabricated foot orthoses,while those in the control group did not wear foot orthoses. Questionnaire survey was conducted 1 week later,and the foot orthoses of those recruits with adverse events were remoulded. The health data of recruits were collected again by questionnaire survey and physical examination 12 weeks later.The primary outcome was the incidence of LLOI. The secondary outcomes included the type of LLOI,the lost training time due to LLOI,the comfort score of the foot orthoses,and the adverse events. Results There were no significant differences in the baseline characteristics between the 2 groups (P>0.05). A total of 76 cases of LLOI was recorded,including 24 cases (12％) in the intervention group and 52 cases (26％) in the control group. Plantar fasciitis was the most common type of LLOI. The lost training time of the intervention group and the control group were 51 d (2.12 d for each one) and 123 d (2.37 d for each one),respectively. The comfort scores of the foot orthoses at 1 week and 12 weeks were 3.76±1.87 and 2.03±1.74,respectively. The incidences of adverse events in 1 week and 3 months were 18％ (36/200) and 5％ (10/200),respectively. The most common adverse event was arch pain. Conclusion VHD prefabricated foot orthoses can reduce the incidence of LLOI and lost training time due to LLOI in recruits,with good wearing comfort and less adverse events.