Forensic medicine has been designated as a first-level discipline,presenting new opportunities and challenges for the development of forensic medicine.Since the 1980s,the establishment of foren-sic medicine discipline and the cultivation of high-level forensic talents have become hot topics in the development of forensic medicine in China.Since the 13th Five-Year Plan,the forensic team of Shanxi Medical University has been aiming at the forefront,proposing the development goals of"Five First-class"and the discipline development path"Six Major Achievements".It has selected benchmark disci-plines,identified gaps in disciplinary development,unified thoughts,formulated completion timelines,concentrated superior resources,assigned tasks to individuals,and created an"Organized Fill-in-the-Blank Format"forensic medicine discipline construction model with the characteristics of the new era.The construction model of forensic medicine has achieved good results in the goals,discipline frame-work,scientific research,talent cultivation,discipline team and platform construction,forming a rela-tively complete discipline construction and management system,and accumulating valuable experience for the construction of first-level discipline and high-level talent cultivation of forensic medicine.

Objective To investigate the protective effects of the ANXA1(Annexin A1)mimetic peptide Ac2-26 on mice with severe heatstroke(HS)and its underlying mechanisms.Methods Twenty-four adult healthy male C57BL/6J mice weighing 20-25 g were randomly divided into four groups using a simple random sampling method:control group(Con group),Con+Ac2-26 group,severe heatstroke group(HS group),and severe heatstroke+Ac2-26 group(HS+Ac2-26 group),with 6 mice in each group.Mice in Con+Ac2-26 group and HS+Ac2-26 group were injected intraperitoneally with Ac2-26(6 mg/kg),and the remaining mice of two groups were injected intraperitoneally with normal saline of equivalent volume.One hour after drug administration,mice in HS group and HS+Ac2-26 group were placed in a high-temperature and high-humidity simulated environment[(37.0±0.5)℃,75%±5%humidity],while mice in Con group and Con+Ac2-26 were kept in a room temperature and humidity environment[(24±0.5)℃and 40±5%humidity]throughout the experiment.The anal temperature of the mice was recorded every 5 minutes;when the anal temperature of mice in HS group and HS+Ac2-26 group reached 42℃,they were removed from the high-temperature environment and placed in a room temperature environment for 6 hours of rewarming,after which blood samples of mice in each group were collected.Flow cytometry was used to detect the proportion of neutrophils and the expression levels of Cd11b and Cd62L(molecules related to neutrophil activation).Enzyme-linked immunosorbent assay(ELISA)was used to measure the plasma levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6),IL-10,and IL-4.Hematoxylin-eosin staining(HE staining)was performed to observe the pathological changes in lung,kidney and liver tissues.Furthermore,RNA sequencing(RNA-seq)was conducted to detect changes in neutrophil gene expression.Results Compared with Con group,Con+Ac2-26 group showed no significant increase in neutrophil proportion,decreased expression of CD62L and CD11b,no significant changes in cytokine levels,and no obvious pathological changes in lung,kidney,or liver tissues.Compared with HS group,the time for mice in HS+Ac2-26 group to reach an anal temperature of 42℃and the time to develop hypothermia after model establishment were both prolonged(P<0.05);the proportion of neutrophils was reduced(P<0.05);the plasma levels of pro-inflammatory cytokines TNF-α and IL-6 were decreased(P<0.05);and the plasma level of anti-inflammatory cytokine IL-10 was increased(P<0.05).HE staining results showed that compared with HS group,HS+Ac2-26 group had a reduced range of inflammatory cell infiltration in lung,kidney,and liver tissues.RNA-seq results revealed that compared with HS group,HS+Ac2-26 group had decreased expression levels of molecules related to the oxidative phosphorylation signaling pathways and neutrophil extracellular trap(NETs).Conclusion Annexin A1 mimetic peptide Ac2-26 may reduce the pro-inflammatory response and alleviate the heatstroke-induced organ histopathologic damage in heatstroke mice by inhibiting oxidative phosphorylation in heat-stressed cells and NETs formation.

Objective To explore the correlation between fasting blood glucose(FBG)level and fractional flow reserve(FFR)in patients with borderline coronary artery disease,and to clarify its potential influence on FFR measurement.Methods From August 2020 to August 2023,the data of 135 patients with coronary atherosclerotic heart disease who received coronary angiography and FFR evaluation in the Fourth Affiliated Hospital of Harbin Medical University were retrospectively collected.According to the exclusion and inclusion criteria,85 cases of borderline diseased vessels of single coronary artery with stenosis degree of 50％-80％were screened out,and they were divided into FBG≥6.1 mmol/L group(47 cases)and FBG＜6.1 mmol/L group(38 cases).The baseline data,angiographic and functional indexes of the two groups were compared,and the correlation between FBG and FFR was analyzed.Results Compared with the FBG＜6.1 mmol/L group,the FBG≥6.1 mmol/L group had a higher proportion of FFR negative results(72.3％vs.23.7％,P＜0.001),and the FFR measurement values were generally increased[0.84(0.80,0.90)vs.0.75(0.68,0.80),P＜0.001],with statistically significant differences.Pearson correlation analysis was performed on all lesions,and FFR＞0.80(negative result)was positively correlated with FBG≥6.1 mmol/L(r=0.484,P＜0.001).Conclusions Among the patients with borderline coronary artery disease(50％-80％stenosis)included in this study,FBG≥6.1 mmol/L is significantly correlated with FFR＞0.80.For patients with borderline coronary lesions with elevated FBG,the influence of blood glucose factors should be carefully considered in clinical interpretation of FFR results.

In this experiment, self-assembled nanoparticles(SANs) were prepared by the pH-driven method, and Her-HCP SAN was constructed by using herpetrione(Her) and Herpetospermum caudigerum polysaccharides(HCPs). The average particle size and polydispersity index(PDI) were used as evaluation indexes for process optimization, and the quality of the final formulation was evaluated in terms of particle size, PDI, Zeta potential, and microstructure. The proposed Her-HCP SAN showed a spheroid structure and uniform morphology, with an average particle size of(244.58±16.84) nm, a PDI of 0.147 1±0.014 8, and a Zeta potential of(-38.52±2.11) mV. Her-HCP SAN significantly increased the saturation solubility of Her by 2.69 times, with a cumulative release of 90.18% within eight hours. The results of in vivo unidirectional intestinal perfusion reveal that Her active pharmaceutical ingredient(API) is most effectively absorbed in the jejunum, where both K_a and P_(app) are significantly higher compared to the ileum(P<0.001). However, the addition of HCP leads to a significant reduction in the P_(app) of Her in the jejunum(P<0.05). Furthermore, the formation of the Her-HCP SAN results in a notably lower P_(app) in the jejunum compared to Her API alone(P<0.001), while both K_a and P_(app) in the ileum are significantly increased(P<0.001, P<0.05). The absorption of Her-HCP SAN at different concentrations in the ileum shows no significant differences, and the pH has no significant effect on the absorption of Her-HCP SAN in the ileum. The addition of the transporter protein inhibitors(indomethacin and rifampicin) significantly increases the absorption parameters K_a and P_(app) of Her-HCP SAN in the ileum(P<0.05,P<0.01), whereas the addition of verapamil has no significant effect on the intestinal absorption parameters of Her-HCP SAN, suggesting that Her may be a substrate for multidrug resistance-associated protein 2 and breast cancer resistance proteins but not a substrate of P-glycoprotein.
Nanoparticles/metabolism* ; Polysaccharides/pharmacokinetics* ; Intestinal Absorption/drug effects* ; Animals ; Rats ; Particle Size ; Drugs, Chinese Herbal/pharmacokinetics* ; Male ; Rats, Sprague-Dawley ; Drug Carriers/chemistry* ; Drug Compounding ; Cucurbitaceae/chemistry*

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Hypertension/pathology* ; Renin-Angiotensin System/drug effects* ; Rats, Inbred SHR ; Oxidative Stress/drug effects* ; Male ; Rats, Inbred WKY ; Blood Pressure/drug effects* ; Myocardium/pathology* ; Rats ; Inflammation/pathology*

OBJECTIVE: To evaluate the immediate effect of Kuanxiong Aerosol (KXA) on perioperative coronary microcirculation in patients with unstable angina (UA) suffering from elective percutaneous coronary intervention (PCI). METHODS: From February 2021 to July 2023, UA inpatients who underwent PCI alone in the left anterior descending (LAD) branch were included. Random numbers were generated to divide patients into the trial group and the control group at a ratio of 1:1. The index of coronary microcirculation resistance (IMR) was measured before PCI, and the trial group was given two sprays of KXA, while the control group was not given. IMR was measured again after PCI, cardiac troponin I (cTnI) and creatine kinase isoenzyme-MB (CK-MB) were detected before and 24 h after surgery, and major cardiovascular adverse events (MACEs) were recorded for 30 days. The data statistics and analysis personnel were blinded. RESULTS: Totally 859 patients were screened, and 62 of them were involved into this study. Finally, 1 patient in the trial group failed to complete the post-PCI IMR and was excluded, 30 patients were included for data analysis, while 31 patients in the control group were enrolled in data analysis. There was no significant difference in baseline data (age, gender, risk factors, previous history, biochemical index, and drug therapy, etc.) between the two groups. In addition, differences in IMR, cTnI and CK-MB were not statistically significant between the two groups before surgery. After PCI, the IMR level of the trial group was significantly lower than that of the control group (19.56 ± 14.37 vs. 27.15 ± 15.03, P=0.048). Besides, the incidence of perioperative myocardial injury (PMI) was lower in the trial group, but the difference was not statistically significant (6.67% vs. 16.13%, P=0.425). No MACEs were reported in either group. CONCLUSIONS KXA has the potential of improving coronary microvascular dysfunction. This study provides reference for the application of KXA in UA patients undergoing elective PCI. (Registration No. ChiCTR2300069831).
Humans ; Percutaneous Coronary Intervention ; Male ; Microcirculation/drug effects* ; Female ; Angina, Unstable/physiopathology* ; Pilot Projects ; Middle Aged ; Aged ; Drugs, Chinese Herbal/pharmacology* ; Aerosols ; Troponin I/blood* ; Coronary Circulation/drug effects* ; Elective Surgical Procedures

Mutations in the cyclin-dependent kinase-like 5 gene (CDKL5) cause a severe neurodevelopmental disorder, yet the impact of truncating mutations remains unclear. Here, we introduce the Cdkl5^492stop mouse model, mimicking C-terminal truncating mutations in patients. 492stop/Y mice exhibit altered dendritic spine morphology and spontaneous seizure-like behaviors, alongside other behavioral deficits. After creating cell lines with various Cdkl5 truncating mutations, we found that these mutations are regulated by the nonsense-mediated RNA decay pathway. Most truncating mutations result in CDKL5 protein loss, leading to multiple disease phenotypes, and offering new insights into the pathogenesis of CDKL5 disorder.
Animals ; Disease Models, Animal ; Mice ; Protein Serine-Threonine Kinases/deficiency* ; Mutation/genetics* ; Epileptic Syndromes/genetics* ; Humans ; Dendritic Spines/pathology* ; Spasms, Infantile/genetics* ; Male ; Seizures/genetics* ; Mice, Inbred C57BL

Objective:To evaluate the clinical efficacy of Tianma Xionglin Zhixuan Tablets in treating hypertension patients with liver yang hyperactivity or comorbid phlegm-stasis syndrome and explore its therapeutic mechanisms through plasma metabolomics.Methods:Thirty-six hypertension patients(4 dropouts)diagnosed with liver yang hyperactivity or phlegm-stasis syndrome were enrolled as the treatment group from June 2022 to September 2023 at the First Affiliated Hospital of Hunan University of Chinese Medicine,while 30 healthy volunteers with balanced constitutions were recruited as the blank group.Plasma samples were collected from patients pre-and post-treatment and from healthy volunteers.Clinical outcomes,including syndrome scores,office blood pressure(BP),and 24-hour ambulatory BP,were recorded.Plasma metabolomic profiling was performed using liquid chromatography-mass spectrometry(LC-MS).Results:Compared with baseline,Tianma Xionglin Zhixuan Tablets significantly reduced traditional Chinese medicine syndrome scores(P＜0.01),office systolic/diastolic BP(P＜0.01),and 24-hour ambulatory BP parameters(24-hour mean BP,daytime/nighttime mean BP;all P＜0.01).Metabolomic analysis identified 45 differential metabolites between the blank group and pretreatment patients,and 64 metabolites altered post-treatment(VIP＞1,P＜0.05).Enrichment analysis of 16 overlapping endogenous metabolites revealed that Tianma Xionglin Zhixuan Tablets primarily modulated arachidonic acid metabolism and sphingolipid metabolism pathways.Conclusion:Tianma Xionglin Zhixuan Tablets demonstrates significant clinical efficacy in hypertension patients with liver yang hyperactivity or phlegm-stasis syndrome,potentially mediated through regulation of arachidonic acid and sphingolipid metabolism.

Objective To explore the correlation between fasting blood glucose(FBG)level and fractional flow reserve(FFR)in patients with borderline coronary artery disease,and to clarify its potential influence on FFR measurement.Methods From August 2020 to August 2023,the data of 135 patients with coronary atherosclerotic heart disease who received coronary angiography and FFR evaluation in the Fourth Affiliated Hospital of Harbin Medical University were retrospectively collected.According to the exclusion and inclusion criteria,85 cases of borderline diseased vessels of single coronary artery with stenosis degree of 50％-80％were screened out,and they were divided into FBG≥6.1 mmol/L group(47 cases)and FBG＜6.1 mmol/L group(38 cases).The baseline data,angiographic and functional indexes of the two groups were compared,and the correlation between FBG and FFR was analyzed.Results Compared with the FBG＜6.1 mmol/L group,the FBG≥6.1 mmol/L group had a higher proportion of FFR negative results(72.3％vs.23.7％,P＜0.001),and the FFR measurement values were generally increased[0.84(0.80,0.90)vs.0.75(0.68,0.80),P＜0.001],with statistically significant differences.Pearson correlation analysis was performed on all lesions,and FFR＞0.80(negative result)was positively correlated with FBG≥6.1 mmol/L(r=0.484,P＜0.001).Conclusions Among the patients with borderline coronary artery disease(50％-80％stenosis)included in this study,FBG≥6.1 mmol/L is significantly correlated with FFR＞0.80.For patients with borderline coronary lesions with elevated FBG,the influence of blood glucose factors should be carefully considered in clinical interpretation of FFR results.