OBJECTIVE: To investigate the effectiveness and preliminary mechanisms of icariin (ICA) in enhancing the reparative effects of adipose-derived stem cells (ADSCs) on skin radiation damagies in rats. METHODS: Twelve SPF-grade Sprague Dawley rats [body weight (220±10) g] were subjected to a single dose of 10 Gy X-ray irradiation on a 1.5 cm×1.5 cm area of their dorsal skin, with a dose rate of 200 cGy/min to make skin radiation damage model. After successful modelling, the rats were randomly divided into 4 groups ( n=3), and on day 2, the corresponding cells were injected subcutaneously into the irradiated wounds: group A received 0.1 mL of rat ADSCs (1×10 ⁷cells/mL), group B received 0.1 mL of rat ADSCs (1×10 ⁷cells/mL)+1 μmol/L ICA (0.1 mL), group C received 0.1 mL of rat ADSCs (1×10 ⁷cells/mL) pretreated with a hypoxia-inducible factor 2α (HIF-2α) inhibitor+1 μmol/L ICA (0.1 mL), and group D received 0.1 mL of rat ADSCs (1×10 ⁷cells/mL) pretreated with a Notch1 inhibitor+1 μmol/L ICA (0.1 mL). All treatments were administered as single doses. The skin injury in the irradiated areas of the rats was observed continuously from day 1 to day 7 after modelling. On day 28, the rats were sacrificed, and skin tissues from the irradiated areas were harvested for histological examination (HE staining and Masson staining) to assess the repair status and for quantitative collagen content detection. Immunohistochemical staining was performed to detect CD31 expression, while Western blot and real-time fluorescence quantitative PCR (qRT-PCR) were used to measure the protein and mRNA relative expression levels of vascular endothelial growth factor (VEGF), platelet-derived growth factor BB (PDGF-BB), fibroblast growth factor 2 (FGF-2), interleukin 10 (IL-10), transforming growth factor β (TGF-β), HIF-2α, and Notch1, 2, and 3. RESULTS: All groups exhibited skin ulcers and redness after irradiation. On day 3, exudation of tissue fluid was observed in all groups. On day 7, group B showed significantly smaller skin injury areas compared to the other 3 groups. On day 28, histological examination revealed that the epidermis was thickened and the dermal fibers were slightly disordered with occasional inflammatory cell aggregation in group A. In group B, the epidermis appeared more normal, the dermal fibers were more orderly, and there was an increase in new blood vessels without significant inflammatory cell aggregation. In contrast, groups C and D showed significantly increased epidermal thickness, disordered and disrupted dermal fibers. Group B had higher collagen fiber content than the other 3 groups, and group D had lower content than group A, with significant differences ( P<0.05). Immunohistochemical staining showed that group B had significantly higher CD31 expression than the other 3 groups, while groups C and D had lower expression than group A, with significant differences ( P<0.05). Western blot and qRT-PCR results indicated that group B had significantly higher relative expression levels of VEGF, PDGF-BB, FGF-2, IL-10, TGF-β, HIF-2α, and Notch1, 2, and 3 proteins and mRNAs compared to the other 3 groups ( P<0.05). CONCLUSION ICA may enhance the reparative effects of ADSCs on rat skin radiation damage by promoting angiogenesis and reducing inflammatory responses through the HIF-2α-VEGF-Notch signaling pathway.
Animals ; Rats, Sprague-Dawley ; Skin/pathology* ; Rats ; Vascular Endothelial Growth Factor A/genetics* ; Basic Helix-Loop-Helix Transcription Factors/genetics* ; Signal Transduction ; Flavonoids/pharmacology* ; Adipose Tissue/cytology* ; Stem Cells/cytology* ; Receptors, Notch/metabolism* ; Radiation Injuries, Experimental/metabolism* ; Wound Healing/drug effects* ; Male

Exosomes are small vesicles commonly found in bodily fluids such as blood, urine, ascites, and breast milk. As essential mediators of intercellular communication, exosomes play pivotal roles in physiological and pathological processes including material transport, signal transduction, homeostasis regulation, immune response, and angiogenesis. They are promising biomarkers for disease diagnosis and key carriers for therapeutic drug delivery. Longitudinal tracking of exosome biodistribution, elucidating their migratory routes and homing effects, determining optimal delivery routes and therapeutic dosages, and evaluating implantation in target tissues are crucial for better understanding their mechanisms of action and guiding clinical applications. Magnetic resonance imaging (MRI), as a non-invasive and repeatable imaging technique, offers an ideal approach for exosome tracking. By labeling exosomes with specific contrast agents or tracers and detecting them via MRI, researchers can trace exosomes in vivo. This facilitates advancements in exosome-based nanomedicine and accelerates the clinical translation of exosome diagnostics and therapeutics.
Exosomes/metabolism* ; Humans ; Magnetic Resonance Imaging/methods* ; Contrast Media ; Animals ; Tissue Distribution

OBJECTIVES: To assess the efficacy and safety of Tiaozhou Ziyin (TZZY) recipe for treatment of premature ovarian insufficiency (POI) and explore the possible mechanisms. METHODS: We used bioinformatics analyses and network pharmacology to identify the main active ingredients in TZZY recipe and their core targets, which were verified by Western blotting. We tested the efficacy and safety of the recipe in 60 POI patients, who were randomized into control group (n=30) with Femoston treatment and TZZY group (n=30) with additional TZZY recipe treatment for 3 menstrual cycles. RESULTS: The core active ingredients of TZZY recipe included kaempferol, β-sitosterol, luteolin, and quercetin. The core targets included SRC, TP53, STAT3, PIK3CA, and MAPK3, which were involved in positive regulation of cell movement and protein phosphorylation, the cancer pathways and the PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had good binding ability with the core targets. In female rat models of POI, TZZY recipe treatment significantly up-regulated ovarian expressions of p-PI3K and p-Akt proteins. In the clinical trial, treatment with Femoston and Femoston plus TZZY recipe both significantly increased E₂ levels and reduced FSH and LH levels and Kupperman scores of the patients, and the combined treatment produced significantly stronger effects. Both treatments increased the number of antral follicles of the patients, but the combined treatment also significantly increased the levels of AMH. CONCLUSIONS The therapeutic mechanism of TZZY recipe for POI involves multiple active ingredients, multiple therapeutic targets and multiple pathways, and activating the PI3K /Akt pathway is one of its main mechanisms of action, to improve ovarian reserve function, alleviate clinical symptoms, and enhance clinical efficacy in POI patients.
Female ; Primary Ovarian Insufficiency/drug therapy* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Animals ; Rats ; Molecular Docking Simulation ; Signal Transduction ; Sitosterols/therapeutic use* ; Kaempferols/therapeutic use*

Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.

Objective:To identify species type and analyze the homology of Brucella in a family cluster infection. Methods:Two patients with brucellosis from the same family who were treated at the First People's Hospital of Lianyungang City, Jiangsu Province in May 2022 were selected as the research subjects. Brucella strains (H4LYG01 and H2LYG02) were isolated through blood culture. The isolated strains were identified for species type and homology analysis using a fully automated microbial mass spectrometry detection system. Molecular typing of the isolated strains was performed using multiple locus variable-number tandem-repeat analysis (MLVA) and multilocus sequence typing (MLST). Results:H4LYG01 and H2LYG02 were both Brucella Maltese, and the credibility scores were 9.745 and 9.627, respectively, and the homology was 100%. The MLVA results showed that the gene loci of H4LYG01 and H2LYG02 were completely identical, with the same genotype. The MLST results showed that the sequence type (ST) of H4LYG01 and H2LYG02 were both ST8 types. Conclusion:The two isolated strains of Brucella from a family with clustered infections are both Brucella Maltese and from the same source.

Objective:To explore the effects of the intervention of ginger baixiao moxibustion combined with probiotics on immune function, liver and kidney function of colorectal cancer patients after surgery, so as to provide a theoretical basis for clinical intervention methods to promote postoperative rehabilitation of patients.Methods:This study was a randomized controlled trial, and 180 patients with colorectal cancer radical resection from the Cancer Hospital of Guangxi Medical University were randomly divided into 4 groups, namely control group, probiotic group, ginger baixiao moxibustion group, and combination group, with 45 cases in each group. The control group was given routine nursing before and after surgery. In the probiotic group, probiotics were used for 3 d in routine preoperative care and 4 d from the first day after surgery. The preoperative routine care of the ginger baixiao moxibustion group was supplemented by ginger baixiao moxibustion for 3 d, and the intervention was carried out on the first day after surgery for 4 d. The combined group was treated with probiotics before and after surgery, and the specific intervention methods were the same as those of the probiotics group and the ginger baixiao moxibustion group. The differences in postoperative immune function, liver and kidney function and and other indexes among the four groups were compared.Results:Forty-five cases were ultimately selected from each of the 4 groups. There were 31 males and 14 females, aged (56.67 ± 10.13) years old in the control group. There were 27 males and 18 females, aged (55.33 ± 13.02) years old in the probiotic group. There were 20 males and 25 females, aged (57.87 ± 12.43) years old in the ginger baixiao moxibustion group. There were 26 males and 19 females, aged (57.67 ± 11.63) years old in the combination group. The IgA at 5 d after the operation in the control group, the probiotic group, the ginger baixiao moxibustion group and the combined group were (1.46 ± 0.42), (1.71 ± 0.49), (1.72 ± 0.58), (1.97 ± 0.72) g/L, and the IgM were (0.96 ± 0.20), (1.13 ± 0.33), (1.11 ± 0.35), (1.18 ± 0.52) g/L, and the IgG were (8.45 ± 1.68), (9.57 ± 1.71), (9.41 ± 2.14), (10.40 ± 2.16) g/L, and the differences among the four groups were statistically significant ( F=6.20, 10.64, 7.69, all P<0.05). The CD3 + values at 5 d after the operation in the control group, the probiotic group, the ginger baixiao moxibustion group and the combined group were 0.616 ± 0.094, 0.671 ± 0.101, 0.653 ± 0.119, 0.723 ± 0.091, and CD4 + were 0.408 ± 0.060, 0.444 ± 0.063, 0.441 ± 0.103, 0.483 ± 0.069, and CD4 +/CD8 + were 2.173 ± 0.715, 2.367 ± 0.963, 2.204 ± 1.137, 2.803 ± 1.064, and the differences among the four groups were statistically significant ( F=8.58, 7.43, 3.93, all P<0.05). The alanine aminotransferases at 5 d after the operation in the control group, the probiotic group, the ginger baixiao moxibustion group and the combined group were (16.22 ± 11.56), (15.87 ± 10.69), (12.91 ± 7.45), (11.31 ± 8.31) U/L, and the aspartate aminotransferases were (26.13 ± 7.97), (25.84 ± 7.89), (25.67 ± 10.85), (21.84 ± 5.51) U/L, and the differences among the four groups were statistically significant ( F=2.71, 2.70, both P<0.05). Conclusions:The combination of ginger baixiao moxibustion and probiotics intervention can effectively improve the immune function of colorectal cancer patients after surgery, and improve the liver function and other indexes of patients to a certain extent, so as to benefit patients.

Objective:To investigate the application value of fecal Syndecan-2 (SDC2) gene methylated SDC2 (m SDC2) detection in colorectal cancer (CRC) screening among urban residents in Guangzhou City. Methods:A cross-sectional study was conducted in Shitan Town, Zengcheng District, Guangzhou City from July to December 2022. A community-based screening program for CRC was conducted among residents aged 40-74 years old. m SDC2 detection was employed in the participants, and those with positive results should be recommended to receive colonoscopy examination. The positive rate of m SDC2 detection, colonoscopy compliance rate, detection rate of intestinal lesions and clinicopathological characteristics were observed. The relationship between cycle threshold (CT) value of m SDC2 and intestinal lesions was explored. Further, the cost-effectiveness of screening was evaluated. Results:A total of 8 189 fecal samples were collected from 8 877 participants with the recovery rate of 92.25%. 8 048 qualified samples were enrolled in this study, consisted of 3 182 males (39.54%) and 4 866 females (60.46%), with the average age of 56 years old (40-74 years). The positive rate of m SDC2 detection was 7.99% (643/8 048), and the compliance rate of colonoscopy was 73.10% (470/643). 20 cases (4.25%) of colorectal cancer, 109 cases (23.19%) of advanced adenoma, 145 cases (30.85%) of non-advanced adenoma, 79 cases (16.81%) of polyps were detected. The detection rate of intestinal lesions was 75.11% and indicated significant differences in gender and age. 20 CRCs included 15 of stage 0-I, 4 of stage Ⅱ-Ⅲ and 1 of unknown stage. The CT value of m SDC2 was negatively correlated with the proportion of advanced colorectal neoplasms ( χ2=16.063, P<0.001). The total cost of the screening was 4.339 5 million yuan, the screening benefit was 28.506 2 million yuan, and the benefit-cost ratio was 6.57. Conclusion:The CRC screening strategy of fecal m SDC2 detection combined with colonoscopy has high colonoscopy compliance and detection rate of intestinal lesions, which is conducive to the detection of early CRCs, and has good cost-effectiveness. This study suggests that this method may be applied to the general CRC screening in China and contribute to the prevention of CRC. The CT value of m SDC2 may have a certain suggestion on the malignant degree of intestinal tumors.

Aim To explore the mechanism of oxidized lipoprotein(a)(oxLp(a))inducing pyroptosis of vascu-lar endothelial cells.Methods After incubating human umbilical vein endothelial cells(HUVEC)with 100 mg/L ox-Lp(a)for 24 hours,Western blot and RT-qPCR was used to detect pyroptosis related proteins,pro-inflammatory cytokines,mitochondrial related proteins NRF1,NRF2,PGC-1α and mitochondrial gene cytochrome b(CYTB),ELISA was used to detect the levels of inflammatory factors,scanning electron microscopy was used to detect cell membrane rup-ture,transmission electron microscopy was used to detect mitochondrial morphology,Hoechst33342/PI staining was used to detect cell apoptosis,MitoSOX probe was used to detect mitochondrial reactive oxygen species(mtROS),Flu-4AM probe was used to detect calcium ions,JC-1 probe was used to detect mitochondrial membrane potential(MMP),and Calcein AM staining was used to detect mitochondrial permeability transition pore(mPTP).Transfecting HUVEC with CYTB overexpressing lentivirus and analyzing its effects on oxLp(a)induced pyroptosis and mitochondrial function.Results After treatment with oxLp(a),the expression of NLRP3,pro-Caspase-1,Caspase-1,GSDMD and GSDMD-N proteins re-lated to pyroptosis were significantly increased(P＜0.05);the protein and mRNA levels of CYTB and pro-inflammatory cy-tokine IL-1β,IL-18 were significantly increased(P＜0.05).Small pores appeared on the cell membrane,the percentage of PI stained positive cells significantly increased(P＜0.05).OxLp(a)significantly inhibited the expression of mito-chondrial related proteins NRF1,NRF2 and PGC-1α,and the expression of mitochondrial gene CYTB,promoted an in-crease in mtROS generation,Ca2+overload,a decrease in ATP levels,a decrease in MMP,an increase in mPTP values,and abnormal mitochondrial morphology.After transfection with pHelper 2.0 lentivirus vector overexpressing CYTB,it was found that oxLp(a)induced HUVEC pyroptosis and mitochondrial morphological and functional abnormalities were par-tially reversed by overexpression of CYTB.Conclusion oxLp(a)promotes mitochondrial morphological and functional abnormalities and induces HUVEC pyroptosis by downregulating CYTB.

Introduction: Time away from training and competition from sport injuries may lead to detrimental effects on muscle strength and endurance. The cross-education effect plays an important role in preserving strength during recovery and rehabilitation; however, the effects have been found to be inconclusive. In addition, the distinct impacts of eccentric and concentric strengthening exercises need to be explored. The objective of this study was to compare the cross-education effects of eccentric and concentric wrist flexor strengthening exercises on hand grip strength among recreational athletes. Methods: A total of 39 recreational athletes aged between 18-25 years old were randomly assigned into two groups of wrist flexor strengthening exercise: eccentric (ECC) and concentric (CON) training groups. The training period for the study was 4 weeks with 3 sessions of strengthening exercises per week. Handgrip strength was measured bilaterally, before and after the intervention using the JAMAR handgrip dynamometer. Results: Significant increases in hand grip strength were observed for the ECC and CON groups in both the trained and untrained hands following 4 weeks of training. However, the handgrip strength between the two groups in the untrained hand was not significantly different (p=0.64). The strength gain in the untrained hand was 9.8% and 10.8%, for ECC and CON groups, respectively. Conclusion: The cross-education effect was significant in improving strength in the untrained hand. There was no difference in strength gains between concentric and eccentric strength training.