High mobility group box 1 (HMGB1), when released extracellularly, plays a pivotal role in the development of spinal cord synapses and exacerbates autoimmune diseases within the central nervous system. In experimental autoimmune encephalomyelitis (EAE), a condition that models multiple sclerosis, the levels of extracellular HMGB1 and interleukin-33 (IL-33) have been found to be inversely correlated. However, the mechanism by which IL-33 deficiency enhances HMGB1 release during EAE remains elusive. Our study elucidates a potential signaling pathway whereby the absence of IL-33 leads to increased binding of P300/CBP-associated factor with HMGB1 in the nuclei of astrocytes, upregulating HMGB1 acetylation and promoting its release from astrocyte nuclei in the spinal cord of EAE mice. Conversely, the addition of IL-33 counteracts the TNF-α-induced increase in HMGB1 and acetylated HMGB1 levels in primary astrocytes. These findings underscore the potential of IL-33-associated signaling pathways as a therapeutic target for EAE treatment.
Animals ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Astrocytes/metabolism* ; Interleukin-33/metabolism* ; HMGB1 Protein/metabolism* ; Acetylation ; Mice, Knockout ; Mice, Inbred C57BL ; p300-CBP Transcription Factors/metabolism* ; Mice ; Spinal Cord/metabolism* ; Cells, Cultured ; Female ; Signal Transduction

Objective:To investigate the correlation between time within the glucose target range(TIR) and hyperuricemia(HUA) in patients with type 2 diabetes mellitus(T2DM).Methods:A total of 215 patients with T2DM in the First Affiliated Hospital of Bengbu Medical College from June 2021 to May 2022 were selected and divided into HUA group and non-HUA group according to serum uric acid level. The clinical characteristics and biochemical indicators of the patients were collected. The association of 72 h glucose monitoring system(FGMS) related indicators TIR, mean blood glucose fluctuation range(MAGE), blood glucose variability(CV), blood glucose standard deviation(SDBG), and mean blood glucose(MBG) with serum uric acid level was analyzed. The influencing factors of T2DM combined with HUA were analyzed with binary logistic regression, and receiver operating characteristic(ROC) curve was drawn to evaluate their predictive values.Results:TIR of HUA group was significantly decreased compared with non-HUA group, while HbA 1C, MAGE, CV, SDBG, and MBG were increased( P<0.001). Spearman correlation analysis showed that serum uric acid levels were negatively correlated with TIR, but positively correlated with MAGE, CV, SDBG, and MBG( P<0.001). After dichotomous logistic regression analysis, TIR was found to be an independent protective factor for T2DM with HUA. The ROC curve results showed that the area under the curve(AUC) of TIR for predicting HUA in T2DM was 0.856(95% CI 0.803-0.909, P<0.001), with the best cut-off value being 64.5%, the sensitivity being 76.8%, and the specificity being 90.3%. Conclusion:TIR in patients with T2DM combined with HUA was significantly decreased. TIR is an independent protective factor for T2DM combined with HUA, and TIR shows a certain predictive value for T2DM combined with HUA.

Objective:To investigate the efficacy and safety of accelerated epithelium-off corneal collagen cross-linking (CXL) in the treatment of corneal ectasia after keratorefractive surgery.Methods:An observational case series study was performed.Twelve patients (22 eyes) diagnosed with corneal ectasia after keratorefractive surgery in the First Affiliated Hospital of Army Medical University were enrolled from January 2016 to December 2018.All the patients received accelerated epithelium-off CXL and were followed up for 12 months.Before and 1 week, 1, 3, 6, and 12 months after the operation, the uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) converted to the logarithm of the minimum angle of resolution (LogMAR) unit were measured.The sphericity, cylindricity, and spherical equivalent were examined by Topcon auto refractor.The maximum keratometry (Kmax) of the front surface, mean keratometry (Km) of the front surface, Km of the back surface, symmetry index of front surface (SIf), symmetry index of back surface (SIb), thinnest corneal thickness (TCT), total aberrations, total high-order aberrations, coma aberration, trefoil aberration and spherical aberration were detected by the Sirius analyzer.The depth of corneal demarcation lines was determined by optical coherence tomography.The intraocular pressure was measured by the non-contact tonometry.The corneal endothelial cell density was assayed by the endothelial cell densitometry.The inflammatory reaction and haze were observed with a slit lamp at different time points after surgery.This study adhered to the Declaration of Helsinki.The study protocol was approved by the First Affiliated Hospital of Army Medical University (No.KY2020063). Written informed consent was obtained from each patient before entering the cohort.Results:Among the 22 eyes of 12 cases, 3 eyes of 2 cases (13.64%) underwent small incision lenticule extraction, and 19 eyes of 10 cases (86.36%) underwent excimer laser in situ keratomileusis.The UCVA (LogMAR), BCVA (LogMAR), cylindricity and spherical equivalent before the operation were 0.61±0.42, 0.24±0.23, (-2.83±2.39)D, (-3.60±2.66)D, which were significantly worse than 0.45±0.31, 0.12±0.15, (-2.11±1.67)D, (-3.12±2.31)D at 12 months after the operation ( t=4.054, 4.956, -3.728, -2.742; all at P<0.05). The front surface Kmax, front surface Km and SIf at 12 months after the operation were (48.37±5.80), (41.49±3.04), (5.36±4.07)D, which were significantly lower than (49.61±5.97), (41.66±2.97), (5.85±4.18)D before the operation ( t=5.949, 2.278, 2.719; all at P<0.05). There was no significant difference in sphericity, Km of the back surface, SIb, TCT, total aberrations, total high-order aberrations, coma aberration, trefoil aberration, spherical aberration, intraocular pressure and endothelial cell density between before and 12 months after the operation (all at P>0.05). Grade 0.5-2 haze occurred in 8 eyes of 4 patients one month postoperatively.After administration of prednisolone acetate eye drops, haze decreased or disappeared 3 months postoperatively, with UCVA and BCVA unchanged.A corneal demarcation line with a depth of (285.40±51.61)μm was found in 11 eyes of 6 cases at 1 month after operation. Conclusions:Accelerated epithelium-off CXL can significantly improve visual acuity, reduce corneal astigmatism and corneal curvature, as well as effectively prevent the progress of corneal ectasia.

Objective:To determine the long-term efficacy and safety of intra-cervical lymphatic immunotherapy (ICLIT) for adult allergic rhinitis (AR) by comparing it with subcutaneous immunotherapy (SCIT).Methods:A total of 100 adult AR patients with dust mite allergy in Department of Otorhinolaryngology, First People′s Hospital of Foshan from Feb 2018 to Dec 2019 were randomly divided into two groups, 50 in SCIT group [including 42 males and 8 females, aging (32.55±9.72) years] and 50 in ICLIT group [including 45 males and 5 females, aging (31.33±9.84) years]. The changes in total symptom score (total system score, TSS), nasal symptom score (total nasal symptom score, TNSS), eye symptom score (total ocular scoring system, TOSS), drug score (total medication score, TMS), and quality of life score of the two groups of patients were evaluated before and after treatment, and the adverse reactions of all patients during the treatment period were recorded. The changes in the level of dust mite specific IgE (sIgE) in the serum were evaluated. GraphPad Prism 9.0 software was used for statistical analysis.Results:In the SCIT group, 38 patients completed treatment and follow-up, with a dropout rate of 24%. In the ICLIT group, 48 patients completed treatment and follow-up, with a dropout rate of only 4%. The scores of TSS, TNSS, TOSS, TMS, and quality of life in the ICLIT group before treatment were 32.1±3.0, 27.3±3.1, 4.8±2.8, 2.3±0.9, and 68.1±28.7, respectively; After 36 months of treatment, the scores were 21.8±11.4, 18.1±9.4, 3.7±2.9, 1.3±1.1, and 36.0±26.7, respectively, which were significantly lower than those before treatment (all P<0.001). After 36 months of treatment, the TSS of the ICLIT group improved by 10.3±11.2 compared to before, while the TSS of the SCIT group improved significantly by 21.9±11.0 compared to before, with statistically significant differences between the groups ( P<0.001). No serious systemic adverse reactions occurred in both groups of patients. Conclusions:ICLIT treatment for adult AR has long-term efficacy, high safety, and high compliance, but its long-term efficacy is not as good as SCIT. ICLIT can be considered as a new complementary option for AR immunotherapy.

ObjectiveTo explore the mechanism of Chenpi Huoxiangtang against diarrhea based on network pharmacology and experimental verification. MethodThe active components and targets of Chenpi Huoxiangtang were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and targets related to diarrhea from GeneCards and Online Mendelian Inheritance in Man （OMIM）. Thereby， the common targets were screened out. The component-target-disease network and protein-protein interaction （PPI） network were constructed with Cytoscape 3.7.1 and STRING. Bioconductor and R language were employed for gene ontology （GO） term enrichment and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment of core targets， and AutoDockTools 1.5.6 and AutoDockVina 1.1.2 for molecular docking. Finally， animal experiment was carried out for verification. ResultA total of 51 active components 226 targets of Chenpi Huoxiangtang and 37 common targets of the medicine and the disease were screened out. The core targets were involved in 1 249 GO terms （P<0.05） and 110 KEGG pathways （P<0.05）， mainly the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， hypoxia inducible factor （HIF）-1， and mitogen-activated protein kinase （MAPK） pathways. Molecular docking suggested that hesperidin and Akt1 showed the highest binding affinity. Animal experiment demonstrated that Chenpi Huoxiangtang significantly alleviated the diarrhea symptoms. The diarrhea index on the first day of administration decreased to 0.92， which was statistically different from that （1.24） of the model group （P<0.05）. The intestinal ink propulsion rate was 70.36%， higher than that （58.20%） in the model group （P<0.01）. Moreover， intestinal peristalsis was improved by the decoction. Enzyme-linked immunosorbent assay （ELISA） indicated the decrease in the levels of interleukin-6 （IL-6） and interleukin-1β （IL-1β） （P<0.05） and increase in the levels of Akt1， epidermal growth factor （EGF）， and epidermal growth factor receptor （EGFR） （P<0.05）. ConclusionThe active components of Chenpi Huoxiangtang mainly regulate PI3K/Akt， MAPK， and other signaling pathways through Akt1， IL-6， IL-1β， EGF， EGFR， and other core targets， thereby relieving diarrhea. This study is expected to lay a basis for the research on the pharmacological mechanism of Citri Reticulatae Pericarpium-Pogostemonis Herba combination and the scientific connotation of their compatibility.

Objective To investigate the nutrient contents of various grains in Hubei Province, and to provide a scientific basis for a balanced diet. Methods Various grains (except potatoes and beans) on the market in Hubei Province were collected. The samples were prepared by peeling and milling, or directly milling, and the nutrient contents were determined according to the national standard methods. With reference to the American nutrient profiling model, protein, dietary fiber, vitamin C, vitamin A, vitamin E, potassium, magnesium, iron and calcium, the nine nutrients were selected as recommended nutrients, and sodium, added sugars and fat were restricted nutrients. On the basis of 100 g for calculation, a nutrient-rich food model (Nutrient-rich foods, NRF_9.3) was established and applied to evaluate the grains. Results The evaluation results showed that wheat and buckwheat grains contained a higher recommended nutrient content than restricted nutrient content, and had higher nutritional value. Among them, quinoa (black) had the highest NRF index of 102.4, indicating the most nutritional value. After peeling, the loss rate of nutrient value (NRF_9.3 index) of various grains was 38.73% to 65.00%. Conclusion It is recommended that people should try to choose whole grains when purchasing grain products.

Objective:To explore the changes of estrogen, androgen and progesterone in serum of male patients with primary gouty arthritis (pGA) and their possible role in the pathogenesis of gout.Methods:The serum, clinical data and laboratory parameters of 266 patients with PGA [including 93 patients with acute gout (AG), 118 patients with intermittent gout (IG), 55 patients with chronic gout (CG)] and 129 healthy controls (HC) were collected. The serum estradiol (E 2), progesterone (P), testosterone (T) and E 2/T were detected by CMIA Expression level. SPSS 17.0 statistical software was used for analysis, Wilcoxon rank sum test was used for comparison of measurement data between groups, and Spearman correlation analysis was used for correlation analysis between variables. Results:① The level of E 2 and T level in the serum of PGA, AG, IG and CG group was lower than that of the HC group [(30±8) pg/ml, (27±7) pg/ml, (31±8) pg/ml, (34±7) pg/ml, (35±10) pg/ml; F=17.770, P<0.05] and [(4.4±1.6) ng/ml, (3.8±1.4) ng/ml, (4.6±1.4) ng/ml, (5.1±2.0) ng/ml, (5.8±1.9) ng/ml; F=23.314, P<0.05], but there was no significant difference between HC group and CG group ( P>0.05), The serum E 2 and T levels in AG group were lower than those in IG and CG groups [(27±7) pg/ml, (31±8) pg/ml, (34±7) pg/ml; F=17.770, P<0.05] and [(3.8±1.4) ng/ml, (4.6±1.4) ng/ml, (5.1±2.0) ng/ml; F=23.314, P<0.05], andthe serum E 2 level in IG group was lower than that in CG group [(31±8) pg/ml, (34±7) pg/ml; F=17.770, P<0.05). The levels of P and E 2/T in HC group were lower than those in pGA and AG group [(0.24±0.10) ng/ml, (0.27±0.11)ng/ml, (0.30±0.15) ng/ml; F=5.124, P<0.05] and [(0.006 6±0.002 2) ng/ml, (0.007 6±0.003 2) ng/ml, (0.008 0±0.003 8) ng/ml; F=3.787, P<0.05), while those in IG and CG group were lower than those in AG group [(0.25±0.09) ng/ml, (0.26±0.08) ng/ml, (0.30±0.15) ng/ml; F=5.124, P<0.05]; ② Spearman correlation analysis showed that E 2 level in pGA group was positively correlated with T and CysC( r=0.310, P<0.01; r=0.164, P=0.008), negatively correlated with MO ( r=-0.133, P=0.030), P level was positively correlated with MO ( r=0.139, P=0.023), T level was positively correlated with Crea and CysC ( r=0.179, P=0.003; r=0.162, P=0.008), negatively correlated with WBC, GR and MO ( r=-0.140, P=0.022; r=-0.173, P=0.005; r=-0.149, P=0.015), E 2/T was positively correlated with apob1 and Glu ( r=0.131, P=0.032; r=0.140, P=0.023). In AG group, E 2 level was positively correlated with T and Crea ( r=0.234, P=0.024; r=0.245, P=0.018), T level was positively correlated with Crea ( r=0.349, P=0.001), and negatively correlated with apob1 ( r=-0.250, P=0.016), and E 2/T was positively correlated with apob1 ( r=0.276, P=0.007). In IG group, E 2 level was positively correlated with T ( r=0.269, P=0.003), and negatively correlated with MO ( r=-0.183, P=0.048), while P level was positively correlated with MO( r=0.204, P=0.027). Conclusion:The expression of E 2 and T in the peripheral blood serum of gout patients decreases significantly, the expression of P and E 2/T increases significantly, and there is a positive correlation between E 2 and T, as well as the inflammatory and glycolipid metabolism indexes of gout patients, suggesting that estrogen, androgen and progesterone may participate in the pathogenesis of gout by regulating the inflammation and metabolism of gout.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with insidious onset, insensitive to chemotherapy and poor prognosis, which make its clinical treatment face an enormous challenge. In recent years, with the rapid development of nanotechnology, increasing kinds of nanomedicine come to the forefront in biomedical fields. Through rational design, nanomedicine can be prepared in suitable size and modified with specific liver targeting ligands. Moreover, various therapeutic agents of different mechanisms can be co-loaded into the same nanosystem, thus achieving the synergistic therapeutic effects towards HCC. Nanomedicine is able to enhance drug bioavailability and liver-targeting effect as well as reduce the side effects to normal tissues, which provide a great potential in HCC therapy. This review summarizes the recent progress in the application of nanomedicine for HCC therapy from two aspects: their liver-targeting design strategies and the recent progress in combination therapy of HCC.

Objective To discuss the ultrasonographic characteristics of schistosomal appendicitis lesions. Methods Among the patients with schistosomal hepatopathy who were discovered by Color Doppler ultrasound in Huzhou Central Hospital from January 2012 to December 2015,50 cases with clear history of schistosomiasis and treatment were chosen as a schistosom?al hepatopathy group,meanwhile,50 normal people,who came from non?endemic areas,without schistosomal hepatopathy and schistosomiasis history were chosen as a control group. The two groups were examined by ultrasound scan of the appendix ,and the data of the largest diameter of the appendix and the thickness of the appendix wall were collected,and the sonographic char?acteristics of their appendixes,such as whether the echo of the appendix wall was even or not,were observed. Results The minimum internal diameter of the appendix cavity and the thickness of the appendix wall of the schistosomal hepatopathy group were(2.090 ± 0.790)mm and(1.332 ± 0.313)mm ,respectively,the former was significantly narrower than that of the control group,while the latter was significantly thicker than that of the control group(t=2.647,-4.526,respectively,both P<0.05). The proportions of those with inhomogeneous echo,indistinctness structure,uneven thickening of the appendix wall,as well as having intestinal contents in the appendix cavity in the schistosomal hepatopathy group were higher than those in the control group(χ2=12.000,18.537,24.008,4.244,respectively,all P<0.05). Conclusions Schistosomal appendicitis lesions have obvious ultrasonographic characteristics under ultrasound. Ultrasound can play an important role in judging whether the appen?dix of schistosomiasis patients is involved and discovering the lesion of appendix early.

Objective To prepare a redox-responsive doxorubicin-loaded nanoparticle,and to study its in vitro realease behavior and targeting effect on heptoma cells.Methods Cystamine was grafted on the side chains of hyaluronic acid with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide catalyst,and then β-cyclodextrin (β-CD) was conjugated on the amine groups of the cystamine by Schiff's base reaction to prepare β-CD modified hyaluronic acid (HACD).The HACD/DOX nanoparticles were prepared by encapsulating DOX into HACD using dialysis method.The drug loading,encapsulation efficiency,particle size and distribution,zeta potential and other physical and chemical properties,as well as in vitro drug release behavior of the HACD/DOX nanoparticles were characterized.The cytotoxicity of HACD/DOX nanoparticles to HepG2 cells was studied by cell counting kit-8 (CCK-8) method.The targeting effect of HACD/DOX nanoparticles on HepG2 cells was studied using flow cytometry and confocal laser scanning microscopy (CLSM).Results HACD were successfully synthesized,which could carry DOX to form uniform homogeneous nanoparticles.The drug loading of DOX in the nanoparticles was (16.1±0.2)％ and the encapsulation efficiency was (64.2±0.9)％.The transmission electron microscope images indicated that the shape of the HACD/DOX nanoparticles was homogeneous sphere.The results of granularity analysis showed that the average size of the HACD/DOX nanoparticles was (203.1 ±2.5) nm with a narrow size distribution (PDI =0.202).The zeta potential of the HACD/DOX nanoparticles was (-29.1±0.8) mV.The in vitro release behavior of the nanoparticles exhibited obvious redox-sensitivity.The results of in vitro cytotoxicity showed that the blank carrier material HACD had no obvious toxicity to hepatoma cells,and the HACD/DOX nanoparticles could effectively kill hepatoma cells with the 0.38 μg/ml half maximal inhibitory concentration (IC50) value at 48 h.Flow cytometry and CLSM results demonstrated that the HACD/DOX nanoparticles could target hepatoma cells through the mediating effect of hyaluronic acid.Conclusions The prepared HACD/DOX nanoparticles have suitable particle size,high drug loading and encapsulation efficiency,and can release DOX under the stimulation of reducing agent.These nanoparticles have obvious targeting effect on hepatoma cells,which is expected to be applied as the drug delivery system of hepatocellular carcinoma (HCC) therapy.