Objective To investigate differential patterns of oxygenated hemoglobin concentration in prefron-tal cortical regions between major depressive disorder patients with or without psychotic symptoms during verbal flu-ency task(VFT)performance using functional near-infrared spectroscopy(fNIRS).Methods A total of 108 pa-tients with major depression who were hospitalized in the psychiatric department of the hospital from July 2023 to April 2024 were selected as the study objects.They were divided into two groups(n=60)with or without psychotic symptoms(n=48).fNIRS devices were used to measure and compare the changes in the relative concentration of cerebral hemoglobin in 52 brain channels between the two groups during VFT.Re-sults Compared with the unaccompanied group,the relative concentration of cerebral oxygenated hemoglobin in channel 13 was higher(0.003±0.001 vs.0.002±0.001),and the relative concentration of cerebral oxygen-ated hemoglobin in channel 33 was lower(0.003±0.001 vs.0.007±0.002),the difference was statistically significant(P＜0.05).There was no significant difference in the relative concentration of oxygenated hemo-globin in other brain areas between the two groups(P＞0.05).Conclusion There are abnormal oxygen activ-ity in brain functional areas associated with psychotic symptoms,and fNIRS technique is helpful for early as-sessment of cerebral aerobic function in depressed patients with psychotic symptoms.

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective:To explore the characteristics of blood lipid profile and its correlation with clinical features and cytokines in patients with active systemic sclerosis (SSc).Methods:In this study, from January 2018 to March 2023, a total of 102 SSc patients visited the Second Hospital of Shanxi Medical University and the First Hospital of Shanxi Medical University were enrolled, among which 57 cases were localized skin type, 25 cases were diffuse skin type, 20 cases were overlap syndrome. At the same time, 89 gender and age-matched health check-up subjects in the Second Hospital of Shanxi Medical University were selected as the healthy control group. The total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were compared between the two groups. According to the blood lipid level, they were grouped into normal blood lipid group and abnormal group, TG elevated group and normal group, HDL-C decreased group and normal group. The association between various lipid groups and organ involvement, modified Rodnan skin score (mRSS), laboratory examination and cytokines were analyzed. Continuous data were analyzed using t-test or Mann-Whitney U test, count data were tested with chi-square test, and Spearman correlation analysis was used for correlation analysis. Results:The level of TG [1.31 (1.04, 1.77) mmol/L vs. 1.05 (0.79, 1.35) mmol/L] and LDL-C [(2.33±0.69)mmol/L vs. (2.12±0.64) mmol/L] in active SSc patients were higher than that in HCs, and the level of TC [(4.27±1.11)mmol/L vs. (4.85±0.98)mmol/L] was lower than that in HCs ( Z=3.821, P<0.001; t=2.171, P=0.031; t=-3.791, P<0.001). Fifty-six (54.9%) SSc patients had dyslipidemia, the incidence of the TG increase and the HDL-C reduction was significantly higher. ESR, mRSS score and renal involvement in the dyslipidemia group were higher than that in normal blood lipid group. mRSS score and the incidence of cardiac and renal involvement were higher in the TG elevated group than that in normal group. TG was positively correlated with the mRSS scores ( r=0.321, P=0.001). The incidence of ESR increase and cardiac involvement was higher in HDL-C decreased group than that in normal group, while anti-Scl-70 positive rate was lower. HDL-C was negatively correlated with the ESR ( r=-0.411, P<0.001). In active SSc patients, levels of IL-2[2.78(2.04, 4.96)pg/ml], IL-6[14.71(7.74,28.38)pg/ml], IL-17[10.73(4.38, 26.62)pg/ml], and IFN-γ[5.40(3.11, 10.45)pg/ml] in the dyslipidemia group were higher than those in normal blood lipid group [IL-2:1.73(0.96, 3.75)pg/ml, Z=2.452, P=0.014; IL-6:6.78(4.38, 9.17)pg/ml, Z=3.726, P<0.001; IL-17:4.46(2.98, 12.53)pg/ml, Z=2.176, P=0.030;IFN-γ:3.76(2.20, 4.87)pg/ml, Z=2.960, P=0.003]. TG was positively associated with IL-2( r=0.358, P=0.002), IL-6( r=0.324, P=0.006), IL-10( r=0.270, P=0.024), IL-17( r=0.279, P=0.019), and IFN-γ( r=0.297, P=0.012)in patients with active SSc. HDL-C was negatively associated with levels of IL-2( r=-0.292, P=0.014), IL-6( r=-0.348, P=0.003), IL-10 ( r=-0.261, P=0.029)and TNF-α( r=-0.251, P=0.036). Conclusion:The incidence of dyslipidemia is higher in active SSc patients than that in HCs, the main manifestations are increased TG and LDL-C and decreased TC and HDL-C. Active SSc patients with dyslipidemia have higher levels of ESR and inflammatory cytokines, higher incidence of cardiac and renal involvement, and relatively severe skin fibrosis, which suggest that abnormal lipid metabolism plays an important role in the development of active SSc and organ involvement.

Objective:To investigate gait alterations in patients with rheumatoid arthritis (RA) complicated with knee joint damage and to explore the potential of using gait analysis to evaluate the effectiveness of precision medical or surgical treatments in RA patients, serving as a reference for future gait-related research.Methods:A total of 45 patients with cumulative knee joint RA and 45 healthy control subjects were recruited from May 2021 to May 2022. Gait analysis and scale scoring were performed to compare gait changes between the two groups. Statistical tests including t-test, Mann-Whitney U, and Pearson Chi-square were used to assess group differences. Results:Compared with the control group, the objective gait indexes of the knee involvement in patients with rheumatoid arthritis were double support time [(523±127)ms and (333±45)ms, t=-9.48, P<0.001], total support time [(904±137) ms and (678±101)ms, t=-8.90, P<0.001], step length [(635±81) ms and (548±56) ms, t=-5.91, P<0.001], walking cycle [(1 273±169) ms and (1 075±104) ms, t=-4.76, P<0.001], the proportion of single support cycle (0.298±0.037 and 0.334±0.015, t=6.06, P<0.001), the proportion of double support cycle (0.408±0.069 and 0.309±0.021, t=-7.90, P<0.001), total support period ratio (0.709±0.035 and 0.628±0.041, t=-10.01, P<0.001), step length [(40±5)cm and (52±4)cm, t=9.02, P<0.001], step length [(77±11)cm and (104±8)cm, t=12.71, P<0.001] and the pace [(0.708±0.168) m/s and (1.050±0.192) m/s, t=8.98, P<0.001] were significantly different. Conclusion:Gait analysis can be utilized for the quantitative evaluation of patients with rheumatoid arthritis (RA), complicated with knee darnage, enabling objective quantification of assessment indicators and offering novel ideas and methodologies for diagnosing and treating of patients with RA.

Objective:To investigate the role and mechanism of leucine-rich α-2-glycoprotein 1 (LRG1) in the fibrosis of human pterygium fibroblasts (HPFs).Methods:A total of 30 nasal primary pterygium tissues from patients who underwent pterygium excision surgery and 30 nasal normal conjunctival tissues from patients who underwent strabismus correction surgery were collected from the First Affiliated Hospital of Harbin Medical University between January 2022 and March 2023, serving as the pterygium group and normal control group, respectively.LRG1 protein expression in both groups was detected by immunofluorescence staining.The mRNA and protein levels of LRG1 and transforming growth factor-β1 (TGF-β1) were evaluated by quantitative real-time PCR (qRT-PCR) and Western blot.Primary HPFs were cultured from excised pterygium tissues using tissue block adhesion method, and cell morphology was observed.Vmentin and cytokeratin were identified by immunofluorescence staining.HPFs were divided into recombinant human LRG1 (rhLRG1) group and blank control group treated with or without 10 μg/ml rhLRG1 for 24 hours, respectively, and cell migration was evaluated via scratch assay.Additionally, HPFs were divided into blank control group, LRG1 overexpression group and LRG1 knockdown group.HPFs in LRG1 overexpression group and LRG1 knockdown group were transfected with LRG1 overexpression plasmids and small interfering RNA for 24 hours, respectively.TGF-β1 mRNA level was evaluated by qRT-PCR and expression of TGF-β1, fibronectin (FN), type Ⅲ collagen (COL3), and α-smooth muscle actin (α-SMA) proteins were evaluated by Western blot.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Harbin Medical University (No.2022IIT026).Written informed consent was obtained from each subject.Results:HPFs were successfully isolated, exhibiting spindle-shaped morphology with whorled arrangement, positive identification for vimentin, and negative immunofluorescence staining for cytokeratin.The migration rate of the rhLRG1 group was (83.01±2.56)%, significantly higher than (50.32±4.97)% of the blank control group ( t=9.59, P<0.001).Immunofluorescence staining results showed that compared with normal conjunctival tissue, LRG1 protein was significantly higher expressed in pterygium tissue and was widely distributed in fibrous connective tissue and epithelial layer.Both mRNA and protein levels of LRG1 and TGF-β1 were significantly higher in the pterygium group than in the normal control group (mRNA: t=10.18, 6.15, both P<0.05.protein: t=6.83, 8.79, both P<0.05).In the LRG1 overexpression group, mRNA level of TGF-β1, and protein levels of FN, COL3 and α-SMA were significantly increased compared with the blank control and LRG1 knockdown groups (all P<0.05). Conclusions:LRG1 promotes fibrosis and enhances the migration ability in HPFs, and its mechanism may be associated with the upregulation of the TGF-β1 signaling pathway.

Objective:To investigate the role and mechanism of leucine-rich α-2-glycoprotein 1 (LRG1) in the fibrosis of human pterygium fibroblasts (HPFs).Methods:A total of 30 nasal primary pterygium tissues from patients who underwent pterygium excision surgery and 30 nasal normal conjunctival tissues from patients who underwent strabismus correction surgery were collected from the First Affiliated Hospital of Harbin Medical University between January 2022 and March 2023, serving as the pterygium group and normal control group, respectively.LRG1 protein expression in both groups was detected by immunofluorescence staining.The mRNA and protein levels of LRG1 and transforming growth factor-β1 (TGF-β1) were evaluated by quantitative real-time PCR (qRT-PCR) and Western blot.Primary HPFs were cultured from excised pterygium tissues using tissue block adhesion method, and cell morphology was observed.Vmentin and cytokeratin were identified by immunofluorescence staining.HPFs were divided into recombinant human LRG1 (rhLRG1) group and blank control group treated with or without 10 μg/ml rhLRG1 for 24 hours, respectively, and cell migration was evaluated via scratch assay.Additionally, HPFs were divided into blank control group, LRG1 overexpression group and LRG1 knockdown group.HPFs in LRG1 overexpression group and LRG1 knockdown group were transfected with LRG1 overexpression plasmids and small interfering RNA for 24 hours, respectively.TGF-β1 mRNA level was evaluated by qRT-PCR and expression of TGF-β1, fibronectin (FN), type Ⅲ collagen (COL3), and α-smooth muscle actin (α-SMA) proteins were evaluated by Western blot.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Harbin Medical University (No.2022IIT026).Written informed consent was obtained from each subject.Results:HPFs were successfully isolated, exhibiting spindle-shaped morphology with whorled arrangement, positive identification for vimentin, and negative immunofluorescence staining for cytokeratin.The migration rate of the rhLRG1 group was (83.01±2.56)%, significantly higher than (50.32±4.97)% of the blank control group ( t=9.59, P<0.001).Immunofluorescence staining results showed that compared with normal conjunctival tissue, LRG1 protein was significantly higher expressed in pterygium tissue and was widely distributed in fibrous connective tissue and epithelial layer.Both mRNA and protein levels of LRG1 and TGF-β1 were significantly higher in the pterygium group than in the normal control group (mRNA: t=10.18, 6.15, both P<0.05.protein: t=6.83, 8.79, both P<0.05).In the LRG1 overexpression group, mRNA level of TGF-β1, and protein levels of FN, COL3 and α-SMA were significantly increased compared with the blank control and LRG1 knockdown groups (all P<0.05). Conclusions:LRG1 promotes fibrosis and enhances the migration ability in HPFs, and its mechanism may be associated with the upregulation of the TGF-β1 signaling pathway.

Objective:To investigate gait alterations in patients with rheumatoid arthritis (RA) complicated with knee joint damage and to explore the potential of using gait analysis to evaluate the effectiveness of precision medical or surgical treatments in RA patients, serving as a reference for future gait-related research.Methods:A total of 45 patients with cumulative knee joint RA and 45 healthy control subjects were recruited from May 2021 to May 2022. Gait analysis and scale scoring were performed to compare gait changes between the two groups. Statistical tests including t-test, Mann-Whitney U, and Pearson Chi-square were used to assess group differences. Results:Compared with the control group, the objective gait indexes of the knee involvement in patients with rheumatoid arthritis were double support time [(523±127)ms and (333±45)ms, t=-9.48, P<0.001], total support time [(904±137) ms and (678±101)ms, t=-8.90, P<0.001], step length [(635±81) ms and (548±56) ms, t=-5.91, P<0.001], walking cycle [(1 273±169) ms and (1 075±104) ms, t=-4.76, P<0.001], the proportion of single support cycle (0.298±0.037 and 0.334±0.015, t=6.06, P<0.001), the proportion of double support cycle (0.408±0.069 and 0.309±0.021, t=-7.90, P<0.001), total support period ratio (0.709±0.035 and 0.628±0.041, t=-10.01, P<0.001), step length [(40±5)cm and (52±4)cm, t=9.02, P<0.001], step length [(77±11)cm and (104±8)cm, t=12.71, P<0.001] and the pace [(0.708±0.168) m/s and (1.050±0.192) m/s, t=8.98, P<0.001] were significantly different. Conclusion:Gait analysis can be utilized for the quantitative evaluation of patients with rheumatoid arthritis (RA), complicated with knee darnage, enabling objective quantification of assessment indicators and offering novel ideas and methodologies for diagnosing and treating of patients with RA.

Interleukin- (IL) 23 drives pathogenic differentiation of Th17 cells via the JAK2-STAT3 signaling pathway, upregulates IL-17A/IL-22 expression, and disrupts intestinal barrier integrity, thereby playing a pivotal role in the pathogenesis of Crohn's disease (CD). IL-23p19 inhibitors—exemplified by risankizumab, mirikizumab, and guselkumab—precisely block this pathway. Key phase 3 trials have demonstrated their efficacy in CD, showing significant clinical benefits in patients refractory to conventional therapies or biologics, with no new safety signals identified. The ultimate treatment goal for CD is deep healing (mucosal-transmural-biochemical composite remission) as defined by STRIDE II. However, current evidence exhibits critical limitations: absence of head-to-head drug comparisons, insufficient data on biologic-experienced subpopulations, and heterogeneous follow-up durations leading to uncertainties in long-term safety. Future studies require standardized head-to-head trials with enhanced subgroup analyses to optimize precision therapeutics.

Interleukin- (IL) 23 drives pathogenic differentiation of Th17 cells via the JAK2-STAT3 signaling pathway, upregulates IL-17A/IL-22 expression, and disrupts intestinal barrier integrity, thereby playing a pivotal role in the pathogenesis of Crohn's disease (CD). IL-23p19 inhibitors—exemplified by risankizumab, mirikizumab, and guselkumab—precisely block this pathway. Key phase 3 trials have demonstrated their efficacy in CD, showing significant clinical benefits in patients refractory to conventional therapies or biologics, with no new safety signals identified. The ultimate treatment goal for CD is deep healing (mucosal-transmural-biochemical composite remission) as defined by STRIDE II. However, current evidence exhibits critical limitations: absence of head-to-head drug comparisons, insufficient data on biologic-experienced subpopulations, and heterogeneous follow-up durations leading to uncertainties in long-term safety. Future studies require standardized head-to-head trials with enhanced subgroup analyses to optimize precision therapeutics.

Objective:To explore the characteristics of blood lipid profile and its correlation with clinical features and cytokines in patients with active systemic sclerosis (SSc).Methods:In this study, from January 2018 to March 2023, a total of 102 SSc patients visited the Second Hospital of Shanxi Medical University and the First Hospital of Shanxi Medical University were enrolled, among which 57 cases were localized skin type, 25 cases were diffuse skin type, 20 cases were overlap syndrome. At the same time, 89 gender and age-matched health check-up subjects in the Second Hospital of Shanxi Medical University were selected as the healthy control group. The total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were compared between the two groups. According to the blood lipid level, they were grouped into normal blood lipid group and abnormal group, TG elevated group and normal group, HDL-C decreased group and normal group. The association between various lipid groups and organ involvement, modified Rodnan skin score (mRSS), laboratory examination and cytokines were analyzed. Continuous data were analyzed using t-test or Mann-Whitney U test, count data were tested with chi-square test, and Spearman correlation analysis was used for correlation analysis. Results:The level of TG [1.31 (1.04, 1.77) mmol/L vs. 1.05 (0.79, 1.35) mmol/L] and LDL-C [(2.33±0.69)mmol/L vs. (2.12±0.64) mmol/L] in active SSc patients were higher than that in HCs, and the level of TC [(4.27±1.11)mmol/L vs. (4.85±0.98)mmol/L] was lower than that in HCs ( Z=3.821, P<0.001; t=2.171, P=0.031; t=-3.791, P<0.001). Fifty-six (54.9%) SSc patients had dyslipidemia, the incidence of the TG increase and the HDL-C reduction was significantly higher. ESR, mRSS score and renal involvement in the dyslipidemia group were higher than that in normal blood lipid group. mRSS score and the incidence of cardiac and renal involvement were higher in the TG elevated group than that in normal group. TG was positively correlated with the mRSS scores ( r=0.321, P=0.001). The incidence of ESR increase and cardiac involvement was higher in HDL-C decreased group than that in normal group, while anti-Scl-70 positive rate was lower. HDL-C was negatively correlated with the ESR ( r=-0.411, P<0.001). In active SSc patients, levels of IL-2[2.78(2.04, 4.96)pg/ml], IL-6[14.71(7.74,28.38)pg/ml], IL-17[10.73(4.38, 26.62)pg/ml], and IFN-γ[5.40(3.11, 10.45)pg/ml] in the dyslipidemia group were higher than those in normal blood lipid group [IL-2:1.73(0.96, 3.75)pg/ml, Z=2.452, P=0.014; IL-6:6.78(4.38, 9.17)pg/ml, Z=3.726, P<0.001; IL-17:4.46(2.98, 12.53)pg/ml, Z=2.176, P=0.030;IFN-γ:3.76(2.20, 4.87)pg/ml, Z=2.960, P=0.003]. TG was positively associated with IL-2( r=0.358, P=0.002), IL-6( r=0.324, P=0.006), IL-10( r=0.270, P=0.024), IL-17( r=0.279, P=0.019), and IFN-γ( r=0.297, P=0.012)in patients with active SSc. HDL-C was negatively associated with levels of IL-2( r=-0.292, P=0.014), IL-6( r=-0.348, P=0.003), IL-10 ( r=-0.261, P=0.029)and TNF-α( r=-0.251, P=0.036). Conclusion:The incidence of dyslipidemia is higher in active SSc patients than that in HCs, the main manifestations are increased TG and LDL-C and decreased TC and HDL-C. Active SSc patients with dyslipidemia have higher levels of ESR and inflammatory cytokines, higher incidence of cardiac and renal involvement, and relatively severe skin fibrosis, which suggest that abnormal lipid metabolism plays an important role in the development of active SSc and organ involvement.