ObjectiveNon-invasive magnetic stimulation technology has been widely used in the treatment of Alzheimer’s disease (AD), but there is a lack of convenient and timely methods for evaluating and providing feedback on the effectiveness of the stimulation, which can be used to guide the adjustment of the stimulation protocol. This study aims to explore the possibility of heart rate variability (HRV) in diagnosing AD and guiding AD magnetic stimulation intervention techniques. MethodsIn this study, we used a 40 Hz, 10 mT pulsed magnetic field to expose AD mouse models to whole-body exposure for 18 d, and detected the behavioral and electroencephalographic signals before and after exposure, as well as the instant electrocardiographic signals after exposure every day. ResultsUsing one-way ANOVA and Pearson correlation coefficient analysis, we found that some HRV indicators could identify AD mouse models as accurately as behavioral and electroencephalogram(EEG) changes (P<0.05) and significantly distinguish the severity of the disease (P<0.05), including rMSSD, pNN6, LF/HF, SD1/SD2, and entropy arrangement. These HRV indicators showed good correlation and statistical significance with behavioral and EEG changes (r>0.3, P<0.05); HRV indicators were significantly modulated by the magnetic field exposure before and after the exposure, both of which were observed in the continuous changes of electrocardiogram (ECG) (P<0.05), and the trend of the stimulation effect was more accurately observed in the continuous changes of ECG. ConclusionHRV can accurately reflect the pathophysiological changes and disease degree, quickly evaluate the effect of magnetic stimulation, and has the potential to guide the pattern of magnetic exposure, providing a new idea for the study of personalized electromagnetic neuroregulation technology for brain diseases.

Objective:To evaluate the effect of ciprofol on intraoperative hypotension in patients undergoing bronchoscopy procedures.Methods:In this randomized controlled study, 112 adult patients of either sex, aged 18-64 yr, with a body mass index of 19.8-28.3 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with estimated operation time of ≥1 h, undergoing elective bronchoscopy procedures, were assigned to one of two groups ( n=56 each) using a random number table method: ciprofol group (C group) and propofol group (P group). All the patients received total intravenous anesthesia. The induction dose of ciprofol was 0.1-0.3 mg/kg, and the maintenance dose was 0.4-1.2 mg·kg -1·h -1 in group C. The induction dose of propofol was 1-3 mg/kg, and the maintenance dose was 4-12 mg·kg -1·h -1 in group P. The primary outcome was the incidence of intraoperative hypotension, and the secondary outcomes were the time of emergence from anesthesia, sleep quality, patients′ and surgeons′ satisfaction with anesthesia, and the incidence of complications within 30 days after surgery. Results:Compared with group P, the incidence of intraoperative hypotension was significantly decreased, and the time of emergence from anesthesia was shortened in group C ( P<0.05). There was no statistically significant difference in secondary outcomes between the two groups ( P>0.05). Conclusions:Ciprofol is superior to propofol in reducing the risk of intraoperative hypotension and facilitates a more rapid emergence from anesthesia in patients undergoing bronchoscopy procedures.

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Objective:To investigate whether exosome-derived microRNA (miR)-877-5p can affect the malignant biological behaviors of glioma cells by regulating transmembrane 4 superfamily member 1 (TM4SF1).Methods:(1) Tumor tissues and corresponding adjacent tissues from 42 patients with glioma who underwent surgical resection in Department of Neurosurgery, the First Affiliated Hospital of Nanyang Medical College from September 2024 to February 2025 were collected. The miR-877-5p and TM4SF1 mRNA expressions in tumor tissues and corresponding adjacent tissues were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the correlation between miR-877-5p and TM4SF1 mRNA expressions in tumor tissues was analyzed by Pearson correlation. (2) HEB, U87, LN229, and U251 cells at the logarithmic growth phase were cultured and their miR-877-5p and TM4SF1 mRNA expressions were detected by qRT-PCR. Exosomes from U87, LN229, and U251 cells were isolated, and their morphology was observed under a transmission electron microscope; protein expressions of CD9, CD63, tumor susceptibility gene 101 (TSG101), and Calnexin in exosomes were detected by Western blotting. The miR-877-5p expression in exosomes of U87, LN229, and U251 cells was detected by qRT-PCR. The diameter of exosomes from LN229 cells was measured using a Malvern Zetasizer particle size and zeta potential analyzer, and the uptake efficiency of exosomes in LN229 cells was detected by flow cytometry. LN229 cells were divided into a normal control group, a miR-877-5p negative control group, a miR-877-5p mimic group, a miR-877-5p mimic+pcDNA empty vector group, and a miR-877-5p mimic+pcDNA-TM4SF1 group; except for the normal control group, the other groups were transfected with corresponding plasmids through exosomes and cultured for 24 hours; and then, miR-877-5p mRNA expression was detected by qRT-PCR; cell viability was detected by CCK-8 assay, cell apoptosis was detected by flow cytometry, cell invasion was detected by Transwell assay, and TM4SF1, Cyclin D1, Bcl-2 associated X protein (Bax), and matrix metalloproteinase 2 (MMP2) protein expressions and expressions of TM4SF1 downstream pathway proteins phosphorylated protein kinase B (p-AKT) and β-catenin were detected by Western blotting. The targeting relation between miR-877-5p and TM4SF1 was validated using a dual-luciferase reporter assay. A U251 cell experiment was performed for universal verification: U251 cells were divided into a normal control group, a miR-877-5p negative control group, a miR-877-5p mimic group, a miR-877-5p mimic+pcDNA empty vector group, and a miR-877-5p mimic+pcDNA-TM4SF1 group; cell apoptosis was detected by flow cytometry, and TM4SF1 protein expression was detected by Western blotting. (3) Eighteen male BALB/c nude mice were randomly divided into a control group, a miR-877-5p mimic group, and a miR-877-5p mimic+pcDNA-TM4SF1 group, with 6 mice in each group; 100 μL LN229 cell suspension, LN229 cell suspension transfected with miR-877-5p mimic, and LN229 cell suspension transfected with miR-877-5p mimic and pcDNA-TM4SF1 were, respectively, subcutaneously injected into the lateral abdomen of nude mice in these 3 groups. After 28 days of feeding, the mass and volume of the transplanted tumors were measured, and the TM4SF1, Cyclin D1, Bax, and MMP2 protein expressions in the transplanted tumors were detected by Western blotting. Results:(1) Compared with that in the corresponding adjacent tissues, miR-877-5p mRNA expression in the tumor tissues was significantly decreased and TM4SF1 mRNA expression was statistically increased ( P<0.05). Correlation analysis showed that the miR-877-5p and TM4SF1 mRNA expressions in the tumor tissues were negatively correlated ( r=-0.966, P<0.001). (2) Compared with those in the HEB cells, statistically decreased miR-877-5p mRNA expression and increased TM4SF1 mRNA expression in U87, LN229, and U251 cells were noted ( P<0.05). Under the transmission electron microscope, the exosomes in glioma cells were all biconcave disc-shaped and had a complete lipid bilayer membrane structure. Western blotting indicated positive CD9, CD63, and TSG101 protein expressions and negative Calnexin protein expression in the exosomes of glioma cells. Flow cytometry results indicated a relatively high uptake efficiency of exosomes in LN229 cells. Compared with that in the U87 and U251 cells, the miR-877-5p mRNA expression in exosomes of LN229 cells was significantly decreased ( P<0.05). The diameter of exosomes in LN229 cells was 80-150 nm. Compared with the miR-877-5p negative control group, the miR-877-5p mimic group had an increased miR-877-5p mRNA expression, decreased cell survival rate (negative control group: [95.43±0.23]%; miR-877-5p mimic group: [51.24±5.67]%), increased cell apoptosis rate ([3.34±0.22]% vs. [35.24±4.17]%), reduced number of invasive cells ([127.33±13.63] cells per high-power field vs.[59.67±6.87] cells per high-power field), downregulated TM4SF1, Cyclin D1 and MMP2 protein expressions, upregulated Bax protein expression, and decreased p-AKT and β-catenin protein expressions, with significant differences ( P<0.05). Compared with the miR-877-5p mimics+pcDNA empty vector group, the miR-877-5p mimic+pcDNA-TM4SF1 group had a decreased miR-877-5p expression, increased cell survival rate (miR-877-5p mimics+pcDNA empty vector group: [56.27±5.24]%; miR-877-5p mimic+pcDNA-TM4SF1 group[75.31±8.13]%), decreased cell apoptosis rate ([36.27±4.42]% vs. [15.37±1.73]%), increased number of invasive cells ([62.67±6.14] cells per high-power field vs. [95.50±10.58] cells per high-power field), upregulated TM4SF1, Cyclin D1 and MMP2 protein expressions, decreased Bax protein expression, and upregulated p-AKT and β-catenin protein expressions, with significant differences ( P<0.05). Dual-luciferase assay results showed that in the plasmids carrying wild-type TM4SF1 sequence, the luciferase activity in the miR-877-5p mimics group was significantly lower than that in the miR-877-5p negative control group ( P<0.05); in the plasmids carrying the mutant TM4SF1 sequence, no significant change in the luciferase activity was noted between the miR-877-5p negative control group and miR-877-5p mimic group ( P>0.05). Universal verification results: in U251 cells, compared with the miR-877-5p negative control group, the miR-877-5p mimic group had a significantly increased cell apoptosis rate and a statistically decreased TM4SF1 protein expression ( P<0.05); compared with the miR-877-5p mimic+pcDNA empty vector group, the miR-877-5p mimic+pcDNA-TM4SF1 group showed significantly decreased apoptosis rate and statistically increased TM4SF1 protein expression ( P<0.05). (3) Compared with the normal control group, the miR-877-5p mimic group had statistically reduced tumor mass and volume, significantly decreased TM4SF1, Cyclin D1 and MMP2 protein expressions, and significantly increased Bax protein expression ( P<0.05). Compared with the miR-877-5p mimic group, the miR-877-5p mimic+pcDNA-TM4SF1 group had significantly increased tumor mass and volume, statistically increased TM4SF1, Cyclin D1 and MMP2 protein expressions, and statistically decreased Bax protein expression ( P<0.05). Conclusion:Exosome-derived miR-877-5p may inhibit the proliferative and invasive capacities of glioma cells and promote cell apoptosis by targetedly inhibiting the TM4SF1 expression, thereby exerting an anti-tumor effect.

Aim To establish the pyroptosis model of rat chondrocytes induced by tumor necrosis factor α(TNF-α)in order to study the effect of lysine acetyl-transferase 7(KAT7)on pyroptosis of chondrocytes.Methods Chondrocytes of rat knee joint were isolated by type Ⅱ collagenase digestion,and were identified by toluidine blue staining and Col Ⅱ immunofluorescence.CCK-8 was used to evaluate cell viability.Western blot was used to detect the expression of pyroptosis-related proteins NLRP3,GSDMD,caspase-8 and KAT7 in cells intervened with TNF-α,adenovirus overexpression of KAT7(KAT7-oe)and KAT7 inhibitor WM-3835.The microstructure of the cells was observed by scanning e-lectron microscopy.Pyroptosis was detected by TUNEL staining,and the expression of pyroptosis-related pro-tein and KAT7 was detected by immunofluorescence.Results Compared with the empty virus group,KAT7-oe inhibited cell viability,promoted the expression of pyroptosis-related proteins,and TNF-α enhanced this effect.At the same time,the expression of KAT7 and pyroptosis-related proteins in the TNF-α stimulation group increased,and WM-3835 reduced the related proteins expression.Electron microscopy showed that KAT7-oe caused cell swelling,deformation,membrane perforation and rupture,while WM-3835 could restore cell morphology.TUNEL staining and immunofluores-cence results also confirmed that KAT7-oe induced chondrocyte pyroptosis,and WM-3835 could down-reg-ulate the fluorescence of pyroptosis-related proteins.Conclusions The expression of KAT7 increases in rat chondrocyte pyroptosis model,and the intervention of KAT7 expression affects signal molecules related to py-roptosis pathway,suggesting that KAT7 may be related to chondrocyte pyroptosis.

Objective:To evaluate the effect of ciprofol on intraoperative hypotension in patients undergoing bronchoscopy procedures.Methods:In this randomized controlled study, 112 adult patients of either sex, aged 18-64 yr, with a body mass index of 19.8-28.3 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with estimated operation time of ≥1 h, undergoing elective bronchoscopy procedures, were assigned to one of two groups ( n=56 each) using a random number table method: ciprofol group (C group) and propofol group (P group). All the patients received total intravenous anesthesia. The induction dose of ciprofol was 0.1-0.3 mg/kg, and the maintenance dose was 0.4-1.2 mg·kg -1·h -1 in group C. The induction dose of propofol was 1-3 mg/kg, and the maintenance dose was 4-12 mg·kg -1·h -1 in group P. The primary outcome was the incidence of intraoperative hypotension, and the secondary outcomes were the time of emergence from anesthesia, sleep quality, patients′ and surgeons′ satisfaction with anesthesia, and the incidence of complications within 30 days after surgery. Results:Compared with group P, the incidence of intraoperative hypotension was significantly decreased, and the time of emergence from anesthesia was shortened in group C ( P<0.05). There was no statistically significant difference in secondary outcomes between the two groups ( P>0.05). Conclusions:Ciprofol is superior to propofol in reducing the risk of intraoperative hypotension and facilitates a more rapid emergence from anesthesia in patients undergoing bronchoscopy procedures.

Aim To establish the pyroptosis model of rat chondrocytes induced by tumor necrosis factor α(TNF-α)in order to study the effect of lysine acetyl-transferase 7(KAT7)on pyroptosis of chondrocytes.Methods Chondrocytes of rat knee joint were isolated by type Ⅱ collagenase digestion,and were identified by toluidine blue staining and Col Ⅱ immunofluorescence.CCK-8 was used to evaluate cell viability.Western blot was used to detect the expression of pyroptosis-related proteins NLRP3,GSDMD,caspase-8 and KAT7 in cells intervened with TNF-α,adenovirus overexpression of KAT7(KAT7-oe)and KAT7 inhibitor WM-3835.The microstructure of the cells was observed by scanning e-lectron microscopy.Pyroptosis was detected by TUNEL staining,and the expression of pyroptosis-related pro-tein and KAT7 was detected by immunofluorescence.Results Compared with the empty virus group,KAT7-oe inhibited cell viability,promoted the expression of pyroptosis-related proteins,and TNF-α enhanced this effect.At the same time,the expression of KAT7 and pyroptosis-related proteins in the TNF-α stimulation group increased,and WM-3835 reduced the related proteins expression.Electron microscopy showed that KAT7-oe caused cell swelling,deformation,membrane perforation and rupture,while WM-3835 could restore cell morphology.TUNEL staining and immunofluores-cence results also confirmed that KAT7-oe induced chondrocyte pyroptosis,and WM-3835 could down-reg-ulate the fluorescence of pyroptosis-related proteins.Conclusions The expression of KAT7 increases in rat chondrocyte pyroptosis model,and the intervention of KAT7 expression affects signal molecules related to py-roptosis pathway,suggesting that KAT7 may be related to chondrocyte pyroptosis.

Objective:To investigate whether exosome-derived microRNA (miR)-877-5p can affect the malignant biological behaviors of glioma cells by regulating transmembrane 4 superfamily member 1 (TM4SF1).Methods:(1) Tumor tissues and corresponding adjacent tissues from 42 patients with glioma who underwent surgical resection in Department of Neurosurgery, the First Affiliated Hospital of Nanyang Medical College from September 2024 to February 2025 were collected. The miR-877-5p and TM4SF1 mRNA expressions in tumor tissues and corresponding adjacent tissues were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and the correlation between miR-877-5p and TM4SF1 mRNA expressions in tumor tissues was analyzed by Pearson correlation. (2) HEB, U87, LN229, and U251 cells at the logarithmic growth phase were cultured and their miR-877-5p and TM4SF1 mRNA expressions were detected by qRT-PCR. Exosomes from U87, LN229, and U251 cells were isolated, and their morphology was observed under a transmission electron microscope; protein expressions of CD9, CD63, tumor susceptibility gene 101 (TSG101), and Calnexin in exosomes were detected by Western blotting. The miR-877-5p expression in exosomes of U87, LN229, and U251 cells was detected by qRT-PCR. The diameter of exosomes from LN229 cells was measured using a Malvern Zetasizer particle size and zeta potential analyzer, and the uptake efficiency of exosomes in LN229 cells was detected by flow cytometry. LN229 cells were divided into a normal control group, a miR-877-5p negative control group, a miR-877-5p mimic group, a miR-877-5p mimic+pcDNA empty vector group, and a miR-877-5p mimic+pcDNA-TM4SF1 group; except for the normal control group, the other groups were transfected with corresponding plasmids through exosomes and cultured for 24 hours; and then, miR-877-5p mRNA expression was detected by qRT-PCR; cell viability was detected by CCK-8 assay, cell apoptosis was detected by flow cytometry, cell invasion was detected by Transwell assay, and TM4SF1, Cyclin D1, Bcl-2 associated X protein (Bax), and matrix metalloproteinase 2 (MMP2) protein expressions and expressions of TM4SF1 downstream pathway proteins phosphorylated protein kinase B (p-AKT) and β-catenin were detected by Western blotting. The targeting relation between miR-877-5p and TM4SF1 was validated using a dual-luciferase reporter assay. A U251 cell experiment was performed for universal verification: U251 cells were divided into a normal control group, a miR-877-5p negative control group, a miR-877-5p mimic group, a miR-877-5p mimic+pcDNA empty vector group, and a miR-877-5p mimic+pcDNA-TM4SF1 group; cell apoptosis was detected by flow cytometry, and TM4SF1 protein expression was detected by Western blotting. (3) Eighteen male BALB/c nude mice were randomly divided into a control group, a miR-877-5p mimic group, and a miR-877-5p mimic+pcDNA-TM4SF1 group, with 6 mice in each group; 100 μL LN229 cell suspension, LN229 cell suspension transfected with miR-877-5p mimic, and LN229 cell suspension transfected with miR-877-5p mimic and pcDNA-TM4SF1 were, respectively, subcutaneously injected into the lateral abdomen of nude mice in these 3 groups. After 28 days of feeding, the mass and volume of the transplanted tumors were measured, and the TM4SF1, Cyclin D1, Bax, and MMP2 protein expressions in the transplanted tumors were detected by Western blotting. Results:(1) Compared with that in the corresponding adjacent tissues, miR-877-5p mRNA expression in the tumor tissues was significantly decreased and TM4SF1 mRNA expression was statistically increased ( P<0.05). Correlation analysis showed that the miR-877-5p and TM4SF1 mRNA expressions in the tumor tissues were negatively correlated ( r=-0.966, P<0.001). (2) Compared with those in the HEB cells, statistically decreased miR-877-5p mRNA expression and increased TM4SF1 mRNA expression in U87, LN229, and U251 cells were noted ( P<0.05). Under the transmission electron microscope, the exosomes in glioma cells were all biconcave disc-shaped and had a complete lipid bilayer membrane structure. Western blotting indicated positive CD9, CD63, and TSG101 protein expressions and negative Calnexin protein expression in the exosomes of glioma cells. Flow cytometry results indicated a relatively high uptake efficiency of exosomes in LN229 cells. Compared with that in the U87 and U251 cells, the miR-877-5p mRNA expression in exosomes of LN229 cells was significantly decreased ( P<0.05). The diameter of exosomes in LN229 cells was 80-150 nm. Compared with the miR-877-5p negative control group, the miR-877-5p mimic group had an increased miR-877-5p mRNA expression, decreased cell survival rate (negative control group: [95.43±0.23]%; miR-877-5p mimic group: [51.24±5.67]%), increased cell apoptosis rate ([3.34±0.22]% vs. [35.24±4.17]%), reduced number of invasive cells ([127.33±13.63] cells per high-power field vs.[59.67±6.87] cells per high-power field), downregulated TM4SF1, Cyclin D1 and MMP2 protein expressions, upregulated Bax protein expression, and decreased p-AKT and β-catenin protein expressions, with significant differences ( P<0.05). Compared with the miR-877-5p mimics+pcDNA empty vector group, the miR-877-5p mimic+pcDNA-TM4SF1 group had a decreased miR-877-5p expression, increased cell survival rate (miR-877-5p mimics+pcDNA empty vector group: [56.27±5.24]%; miR-877-5p mimic+pcDNA-TM4SF1 group[75.31±8.13]%), decreased cell apoptosis rate ([36.27±4.42]% vs. [15.37±1.73]%), increased number of invasive cells ([62.67±6.14] cells per high-power field vs. [95.50±10.58] cells per high-power field), upregulated TM4SF1, Cyclin D1 and MMP2 protein expressions, decreased Bax protein expression, and upregulated p-AKT and β-catenin protein expressions, with significant differences ( P<0.05). Dual-luciferase assay results showed that in the plasmids carrying wild-type TM4SF1 sequence, the luciferase activity in the miR-877-5p mimics group was significantly lower than that in the miR-877-5p negative control group ( P<0.05); in the plasmids carrying the mutant TM4SF1 sequence, no significant change in the luciferase activity was noted between the miR-877-5p negative control group and miR-877-5p mimic group ( P>0.05). Universal verification results: in U251 cells, compared with the miR-877-5p negative control group, the miR-877-5p mimic group had a significantly increased cell apoptosis rate and a statistically decreased TM4SF1 protein expression ( P<0.05); compared with the miR-877-5p mimic+pcDNA empty vector group, the miR-877-5p mimic+pcDNA-TM4SF1 group showed significantly decreased apoptosis rate and statistically increased TM4SF1 protein expression ( P<0.05). (3) Compared with the normal control group, the miR-877-5p mimic group had statistically reduced tumor mass and volume, significantly decreased TM4SF1, Cyclin D1 and MMP2 protein expressions, and significantly increased Bax protein expression ( P<0.05). Compared with the miR-877-5p mimic group, the miR-877-5p mimic+pcDNA-TM4SF1 group had significantly increased tumor mass and volume, statistically increased TM4SF1, Cyclin D1 and MMP2 protein expressions, and statistically decreased Bax protein expression ( P<0.05). Conclusion:Exosome-derived miR-877-5p may inhibit the proliferative and invasive capacities of glioma cells and promote cell apoptosis by targetedly inhibiting the TM4SF1 expression, thereby exerting an anti-tumor effect.

Objective To explore the context and hotspot changes of forensic mixed stain research through bibliometric approach.Methods The literature of forensic mixed stain included in the core col-lection of Web of Science database from 2011 to 2022 were collected as the study object,and the an-nual publication number,countrie(region),institution,journal,keywords,etc.were bibliometrically and visually analyzed using the R-based Bibliometrix 1.1.6 package and VOSviewer 1.6.18 software.Re-sults A total of 732 articles on forensic mixed stain were included from 2011 to 2022,with the an-nual number of articles published and the annual citation frequency showing a steady increase year by year.Among the 59 countries(regions)with the most published articles,the United States ranked first with 246 articles,followed by China with 153 articles.The literature came from 104 journals,and the total number of articles published in the top 10 journals was 633.FORENSIC SCI INT GENET ranked first with 307 articles.Visual analysis using VOSviewer software showed that keywords could be divided into four research clusters,namely the genetic marker development group(blue),the mixed stain typing analysis theory group(red),the sequencing analysis group(yellow),and the case sample research group(green).It can be divided into four development stages in terms of different time peri-ods:early development(2011-2013),middle development(2014-2016),rapid development(2017-2020)and latest development(2021-2022).Conclusion The number of publications by domestic and foreign scholars in the study of mixed stain in forensic science is showing a relatively stable trend.Machine learning,next generation sequencing and other research have been the hottest topics that have attracted the most attention in recent years,which is expected to further develop the theory of mixed stain typing and sequencing analysis in forensic mixed stain research.

Objective To explore the mechanism of Angelica Sinensis polysaccharide(ASP)promoting donor bone marrow transplantation(BMT)to reconstruct hematopoietic function of receptor mice by regulating bone marrow stromalcells(BMSCs).Methods Bone marrow mononuclear cells(BMMNCs)of male C57BL/6J mice aged 8-10 weeks were separated,purified and transplanted into female receptor mice of the same age.On the ninth day,receptor mice BMMNCs were separated,purified and transplanted again into female receptor mice.The transplanted receptor mice were divided into control group:sham irradiation;Irradiation(IR)group:a whole-body irradiation with a total dose of 8.0 Gy X-ray;BMT group:the receptor mice treated in the same way as the IR group and transplanted BMMNCs(5×106 cells)from male donor via the tail vein;BMT+ASP group:the receptor mice treated in the same way as the BMT group,and injected ASP[100 mg/(kg·d)×9]by intraperitoneal route from the first day of transplantation.Changes in body weight and survival rate of mice were recorded during modeling,receptor mice BMMNCs were collected to detect sex-determining region of Y(SRY)gene after building model,peripheral blood indexes,the number of BMMNCs in femur and histopathology of bone marrow were detected;BMSCs in receptor mice was separated and purified,BMSCs adhesion ability was observed,proliferation ability was detected by 5-ethynyl-2-deoxyuridine(EdU);The level of reactive oxygen species(ROS),the activity of superoxide dismutase(SOD)and the content of malondialdehyde(MDA)in BMSCs were detected;The levels of granulocyte-macrophage colony-stimulating factor(GM-CSF),stem cell factor(SCF),insulin-like growth factor 1(IGF-1)in culture supernatant of BMSCs were determined,CFU-Mix was counted after BMMNCs co-cultured with receptor BMSCs in each group for 48 hours;The expression of Notch signaling pathway related genes(Notch1,Jagged1,Hes1)in BMMNCs were measured by Real-time PCR.Results All mice in IR group were died,the body weight loss in BMT+ASP group was not obvious.The SRY gene was detected in the receptor female mice BMMNCs.Peripheral blood indexes and the number of BMMNCs were not significantly decreased in BMT+ASP group receptor mice,and bone marrow histopathological injury was reduced.ASP promoted the proliferation of BMSCs,decreased the contents of ROS and MDA,and increased the activity of SOD in BMSCs.ASP promoted the secretion of SCF,GM-CSF and IGF-1 in BMSCs,and increased CFU-Mix yield of BMMNCs co-cultured with receptor BMSCs.ASP increased the expression of Notch1,Jagged1 and Hes1 mRNA in BMMNCs.Conclusion The mechanism of ASP promoting receptor hematopoietic function reconstruction is related to reducing the oxidative stress damage of hematopoietic microenvironment,improving the secretion of hematopoietic growth factors in BMSCs,and regulating Notch signaling pathway.