Thymocyte selection-associated high mobility group box (TOX), a member of the high mobility group protein super-family, plays an important role in T cell development, functional maintenance, and exhaustion. It has been recently found that TOX exerts critical immunoregulatory functions during pathogen infections, and TOX expression is strongly associated with the intensity and tolerance of host immune responses. This review systematically summarizes the structural and functional features of TOX and focuses on its expression dynamics, mechanisms of action, and immunomodulatory effects during viral, bacterial, and parasitic infections, which provides a theoretical support to better understanding of the role of TOX in infectious diseases and provides new insights into development of potential immunotherapeutic strategies targeting TOX.

BACKGROUND: The association between uric acid-albumin ratio (UAR) with different diseases has been evaluated before. However, the association between UAR with spontaneous reperfusion (SR) in patients with ST-segment elevation myocardial infarction (STEMI) has not been explored. METHODS: STEMI patients admitted to our department and underwent primary coronary angiography between 1^st November 2018 and 31^st December 2020 were retrospectively enrolled. The patients were divided into the SR group and the non-SR group according to the index coronary angiography results. The association between UAR and SR was evaluated by uni-variable and multi-variable logistic analysis. Receiver operating characteristic curve analysis was used to determine the optimum cut-off level of UAR in predicting SR. RESULTS: Three hundred and fifty-seven patients were finally enrolled in our study, 55 patients were divided into the SR group and 302 patients were divided into the non-SR group. In uni-variable analysis, patients with SR were older (P = 0.032), with higher red blood cell distribution width (P < 0.001) and red blood cell distribution width-to-platelet ratio (P < 0.001), higher level of C-reactive protein (P = 0.046), higher level of uric acid (P < 0.001) compared with patients without SR. Patients with SR had a lower level of platelets (P = 0.008), lower level of on-admission B-type natriuretic peptide (P < 0.001). As for the level of UAR, STEMI patients with SR had significantly higher levels of UAR compared with STEMI patients without SR [11.1 (8.9-13.4) vs. 8.3 (6.6-10.0), P < 0.001]. Further multi-variable logistic analysis reveals that UAR was the independent risk factor of SR in different models after adjusting different variables. Receiver operating characteristic analysis showed that UAR had good predictive value in SR (AUC = 0.75, 95% CI: 0.702-0.794, P < 0.01). CONCLUSIONS Our study shows that UAR is an independent risk factor for predicting SR in STEMI patients.

Objective:To conduct a comparative analysis of the radiation damage to zebrafish embryos and the associated biological mechanism after ultra-high dose rate (FLASH) and conventional dose rate irradiation.Methods:Zebrafish embryos at 4 h post-fertilization were exposed to conventional and FLASH irradiation (9 MeV electron beam). The mortality and hatchability of zebrafish after radiation exposure were recorded. Larvae at 96 h post-irradiation underwent morphological scoring, testing of reactive oxygen species (ROS) levels, and analysis of changes in oxidative stress indicators.Results:Electron beam irradiation at doses of 2-12 Gy exerted subtle effects on the mortality and hatchability of zebrafish embryos. However, single high-dose irradiation (≥ 6 Gy) could lead to developmental malformation of larvae, with conventional irradiation showing the most significant effects ( t = 0.87-9.75, P < 0.05). In contrast, after FLASH irradiation (≥ 6 Gy), the ROS levels in zebrafish and its oxidative stress indicators including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were significantly reduced ( t = 0.42-15.19, P < 0.05). There was no statistically significant difference in ROS levels in incubating solutions after conventional and FLASH irradiation ( P > 0.05). Conclusions:Compared to conventional irradiation, FLASH irradiation can reduce radiation damage to zebrafish embryos, and this is in a dose-dependent manner. The two irradiation modes lead to different oxidative stress levels in zebrafish, which might be a significant factor in the reduction of radiation damage with FLASH irradiation.

Objective:To analyze the clinical characteristics of patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR), and to explore the risk factors leading to poor prognosis.Methods:The clinical data of 95 patients with ECPR admitted to the First Affiliated Hospital of Zhengzhou University from January 2020 to May 2023 were retrospectively analyzed. According to the survival status at the time of discharge, the patients were divided into the survival group and death group. The difference of clinical data between the two groups was compared to explore the risk factors related to death and poor prognosis. Risk factors associated with death were identified by Binary Logistic regression analysis. Results:A total of 95 patients with ECPR were included in this study, 62 (65.3%) died and 33 (34.7%) survived at discharge. Patients in the death group had longer low blood flow time [40 (30, 52.5) min vs. 30 (24.5, 40) min ] and total cardiac arrest time[40 (30, 52.5) min vs. 30(24.5, 40) min], shorter total hospital stay [3 (2, 7.25) d vs. 19 (13.5, 31) d] and extracorporeal membrane oxygenation (ECMO) assisted time [26.5 (17, 50) h vs. 62 (44, 80.5) h], and more IHCA patients (56.5% vs. 33.3%) and less had spontaneous rhythm recovery before ECMO (37.1% vs. 84.8%). Initial lactate value [(14.008 ± 5.188) mmol/L vs.(11.23 ± 4.718) mmol/L], APACHEⅡ score [(30.10 ± 7.45) vs. (25.88 ± 7.68)] and SOFA score [12 (10.75, 16) vs. 10 (9.5, 13)] were higher ( P< 0.05). Conclusions:No spontaneous rhythm recovery before ECMO, high initial lactic acid and high SOFA score are independent risk factors for poor prognosis in ECPR patients.

Objective To investigate the association between four single nucleotide polymorphisms(SNP)(rs9340 in MAPK1,rs14804 in NRAS,rs712 and rs7973450 in KRAS)in the 3'UTR of ERK1/2 signaling pathway-related genes and non-small cell lung cancer(NSCLC).Methods A total of 478 NSCLC patients and 480 healthy controls were enrolled in this study.Four SNPs were genotyped by using TaqMan assays.The association between the four SNPs and NSCLC was analyzed.Results The distribution frequency difference of the allele of rs9340 was statistically significant between the control group and the non-small cell squamous cell carcinoma(SCC)group(P = 0.009),suggesting that the G allele of rs9340 may be a protective factor for non-small cell lung squamous cell carcinoma(OR = 0.67,95%CI:0.50～0.91).In addition,in the<50 years age group,the distribution frequency difference of the allele of rs9340 was statistically significant between the control group and the NSCLC group(P = 5.07×10-4),indicating that the G allele of rs9340 may be a protective factor for NSCLC(OR = 0.46,95%CI:0.29～0.72).Conclusion The SNP rs9340 in MAPK1 may be associated with the risk of NSCLC.

Objective To investigate the in vitro anti-inflammatory effects of Sophora davidii Hance leaves total alkaloids(SDLTAs)and possible molecular mechanisms.Methods The lipopolysaccharide(LPS)-induced inflammation model of RAW264.7 cells was used,and different concentrations of SDLTAs(50,100 and 200 μg/mL)were administered,and the effect of SDLTAs on cellular NO expression was detected by the Griess method;ELISA method was used to detect the effect of SDLTAs on the expression of IL-6,TNF-α and IL-1β;The expression of iNOS,NF-κB p65 and IκBα mRNA was detected by RT-qPCR;Western blotting was used to detecte the expres-sion of p-p38,p-p65 and p-JNK in the cells and NF-κB p65 in the nucleus.Results SDLTAs could significantly inhibit the LPS-induced inflammatory response in RAW264.7 cells.SDLTAs significantly decreased the secretion of NO,IL-6,TNF-α and IL-1β in cells(P<0.01),and significantly decreased the mRNA expressions of iNOS,NF-κB p65 and IκBα in cells(P<0.01).Significantly decreased the protein expression of p-p38,p-p65 and p-JNK in cells and NF-κB p65 in nucleus(P<0.01).Conclusion SDLTAs can exert anti-inflammatory effects by regulating the MAPK/NF-κB signalling pathway.

This study aims to establish a quality grading standard that combines the conventional quality evaluation based on morphological characteristics of traditional Chinese medicine with the modern quality evaluation. Based on the existing standards and market circulation of Isatidis Radix, the diameter and color of Isatidis Radix decoction pieces were selected as the appearance traits for preliminary grading. The effects of internal quality indexes such as moisture, total ash, acid-insoluble ash, ethanol-soluble extractives, and 9 water-soluble components on different grades of decoction pieces were comprehensively compared, and the key grading indexes were determined by t-test. The relevance between appearance traits and the internal quality indexes was investigated by multi-dimensional statistical analyses such as correlation analysis, principal component analysis(PCA), orthogonal partial least squares-discriminant analysis(OPLS-DA), and hierarchical cluster analysis(HCA). Furthermore, the fluorescent substrate was employed to investigate the inhibitory effects of different grades of Isatidis Radix decoction pieces on the neuraminidase of influenza virus. The rationality of the selected grading index components was verified by network pharmacology. The results showed that the diameter of decoction pieces had significantly positive correlations with other index components except moisture. Considering the existing commodity specifications, grading standards, and actual market circulation of Isatidis Radix, the quality grading standard of Isatidis Radix decoction pieces was developed with diameter as the appearance trait and(R,S)-goitrin as the limit index component of being qualified. On this basis, the content of ethanol-soluble extractives, total sinigrin, and total nucleoside were selected for quality grading. The in vitro enzyme activity evaluation showed that the first grade of Isatidis Radix decoction pieces had stronger inhibitory effect on the neuraminidase of influenza virus, and the network pharmacology results showed that the selected index components for quality grading had significant correlations with influenza. This study established a quality grading standard combining appearance traits and internal quality indexes, which provides a scientific basis for improving the existing grading standards and the price and quality of Isatidis Radix decoction pieces.
Isatis/chemistry* ; Plant Roots/chemistry* ; Drugs, Chinese Herbal/standards* ; Network Pharmacology ; Neuraminidase/antagonists & inhibitors* ; Quality Improvement/standards* ; Viral Proteins

AIM: To investigate the efficacy of epithelial-off accelerated corneal cross-linking(CXL)in the treatment of advanced keratoconus.METHODS: A retrospective study was performed on data collected from 32 patients(43 eyes)with advanced keratoconus who underwent epithelial-off accelerated CXL at Ningxia Eye Hospital from April 2020 to December 2021. Slit-lamp, intraocular pressure, uncorrected visual acuity(UCVA), corrected visual acuity, specular microscope, Pentacam and Corvis ST were tested before and at 1, 3 and 6mo after surgery. Preoperative and postoperative corneal condition, UCVA, best corrected visual acuity(BCVA)and the values of corneal endothelial, maximum keratometry(Kmax), thinnest corneal thickness(TCT), anterior and posterior surfaces of the cornea K1, K2, biomechanically corrected intraocular pressure(bIOP), applanation time 1(A1T), applanation length 1(A1L), applanation velocity 1(A1V), applanation time 2(A2T), applanation length 2(A2L), applanation velocity 2(A2V), highest concavity deformation amplitude(HCDA), radius at highest curvature(HCR), highest concavity peak distance(HCPD)and stiffness parameter at first applanation(SP-A1)were recorded.RESULTS: There were differences between UCVA(LogMAR; 1.06±0.49, 0.78±0.39)and BCVA(LogMAR; 0.48±0.34, 0.38±0.29)before and at 6mo after surgery(P<0.05), but there were no differences in corneal endothelial cells(2917.39±288.38 vs. 2959.19±336.27 cells/mm2, P=0.477). There were differences among Kmax, TCT, anterior surface K1 and K2 and posterior surface K1 before and after surgery(P<0.05), and all increased at 1mo after surgery then returned to preoperative level at 3mo after surgery, while there was no difference in the posterior K2. Furthermore, there were statistical significance in A1T, HCPD and SP-A1 before and after surgery(P<0.05), while there were no statistical significance in A1L, A1V,A2T, A2L, A2V, HCDA, HCR and bIOP(P>0.05).CONCLUSION: Epithelial-off accelerated CXL can prevent the progression of keratoconus within half year after surgery, and it has certain safety.

Objective:To compare the radiation chemistry effects on water molecules after ultra-high dose rate (FLASH) and conventional irradiation.Methods:Both FLASH and conventional irradiation were applied to ultrapure water, with the hydroxyl radical yield in the homogeneous phase detected using electron paramagnetic resonance (EPR) and the hydrogen peroxide (H 2O 2) yield in the diffusion phase analyzed uuxing fluorescence probe. The liposome model was then established to investigate the radiation chemistry effect of FLASH and conventional irradiation in inducing lipid peroxidation. Results:Radiation chemistry reactions were observed in water molecules after irradiation. In the homogeneous phase, the yield of free radicals using FLASH irradiation is similar to those from conventional irradiation ( P>0.05). In the diffusion phase, the amount of H 2O 2 produced by FLASH irradiation was significantly lower than those from conventional irradiation ( t=0.49-12.81, P<0.05). The liposome model confirmed that conventional irradiation could significantly induce lipid peroxidation through the radiation chemistry effect in water molecules as compared with FLASH irradiation ( t=0.31-11.73, P<0.05). Conclusions:The radiation chemistry effect in water molecules after FLASH irradiation was significantly lower than that from conventional irradiation. This could be one of the mechanisms of FLASH effect.

Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor, mostly benign, and malignant is rare. In this paper, we report a 71-year-old male patient with left renal tumor and a 59-year-old patient with right renal tumor who underwent laparoscopic partial nephrectomy and laparoscopic radical total right nephrectomy, respectively. Postoperative pathology showed benign PEComa and malignant PEComa, respectively. Two years and 10 months of follow-up were given to the benign patient and the malignant patient after surgery, and both patients were in good general condition with no tumor recurrence or metastasis.