Local anesthetics (LAs), such as articaine (AT), exhibit limited efficacy in inflammatory environments, which constitutes a significant limitation in their clinical application within oral medicine. In our prior research, we developed AT-17, which demonstrated effective properties in chronic inflammatory conditions and appears to function as a novel oral LA that could address this challenge. In the present study, we further elucidated the beneficial effects of AT-17 in acute inflammation, particularly in oral acute inflammation, where mitochondrial-related apoptosis played a crucial role. Our findings indicated that AT-17 effectively inhibited lipopolysaccharide (LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro. This process involved the inhibition of mitochondrial reactive oxygen species (mtROS) production and the subsequent activation of the NRF2 pathway. Most notably, improvements in mitochondria-related apoptosis were key contributors to AT-17's inhibition of voltage-gated sodium channels. Additionally, AT-17 was shown to reduce mtROS production in nerve cells through the Na⁺/NCLX/ETC signaling axis. In conclusion, we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis. This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.

Objective:To construct novel radiotracers targeting CD36 and evaluate their stabilities and targeting specificities.Methods:ABT-510, an anti-angiogenic peptide that bound CD36, served as the active scaffold for the synthesis of precursor molecules BQ01, BQ02 and BQ03. These precursors were subsequently labeled with 68Ga to yield the tracers 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03, whose radiochemical purities were determined by radio-high-performance liquid chromatography. A systematic characteristics of the radiochemical and biological profiles were performed, including in vitro stability, lipid water partition coefficient (log P), target-binding affinity, pharmacokinetic behaviour, microPET/CT imaging on U87MG tumor bearing mice, biodistribution, and phosphor-screen autoradiography. The tumor/muscle ratios of three probes were compared by one-way analysis of variance (post-hoc tests with Tukey method). Results:The radiochemical purities of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 were all over 95%, and the radiotracers all remained stable in PBS and serum in vitro. The log P values of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 were -3.81±0.08, -3.60±0.03 and -3.85±0.03 respectively, indicating hydrophilicity; and blood clearance half-lives in vivo were (25.6±0.3), (38.2±0.2) and (17.5±0.2) min respectively, demonstrating rapid elimination. 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 displayed high binding affinities toward U87MG cells, with inhibition constants ( Ki) of (4.30±0.63), (3.80±0.24) and (2.61±0.31)nmol/L, respectively. MicroPET/CT demonstrated marked tumor accumulation of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 at 0.5 h after administration in U87MG tumor bearing mice, with SUV max of 0.68±0.09, 0.70±0.09 and 0.89±0.05. Biodistribution results showed the tumor uptakes of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 were (0.35±0.09), (0.53±0.01) and (0.63±0.06) percentage activity of injection dose per gram of tissue (%ID/g), respectively. The tumor/muscle ratio of 68Ga-BQ03 was significantly higher than that of 68Ga-BQ01 or 68Ga-BQ02 ( F=161.50, all P<0.001). Conclusions:Three CD36-targeted radiotracers demonstrate good stability, strong binding affinity, and high tumor uptake. Among them, 68Ga-BQ03 shows the best imaging performance and holds promise for the precise diagnosis of CD36-positive malignant tumors.

Sarin(GB)is a typical representative of nerve agents with high toxicity,and very low amount can cause death.GB can cause water and atmospheric environment poisoning,so the detection of GB in water and air is of great significance.In this work,a colorimetric sensor array(CSA)based on GB inhibition of cholinesterase activity was constructed to detect GB with high selectivity.A 4×4 colorimetric array was constructed using acetylcholinesterase(AChE),butyryl cholinesterase(BuChE)and the corresponding substrate acetylthiocholine iodide(S-ACh),butyryl thiocholine iodide(S-BCh),acetylcholine chloride(ACh),butyryl choline chloride(BCh)and 2,6-dichloroindophenol ethyl ester(DCIE).The linear curve of the sensor was Y=131.3×lgC+271.6(R2=0.997),where Y was the array response Euclidean distance,C was the concentration of GB(mg/L),the linear range was 0.03?0.32 mg/L,and the detection limit was 27.6 μg/L.The method could effectively distinguish chemical warfare agents(CWA)such as VX,Soman(GD),mustard gas(HD),Louie reagent(L),and had high anti-interference ability,sensitivity and good repeatability.It was successfully applied to the detection of GB in simulated water and simulated air samples,and the sample recovery rate was 97.2% ?100.9%.This method would be potentially applied to the field rapid detection of nerve agents.

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 develop and validate machine learning models for predicting the cumulative live birth rate (CLBR) following in vitro fertilization (IVF) and to analyze key predictive features using SHAP values. Methods:This retrospective study included data from patients who underwent IVF-embryo transfer at the Department of Reproductive Medicine, Baoding Maternal and Child Health Hospital, between January 2017 and December 2022. Patients were categorized into two groups based on live birth outcome: the live birth group ( n=1 036) and the non-live birth group ( n=756). The dataset was randomly divided into a training set and a validation set in a ratio of 7∶3. Five algorithms were utilized for model development: logistic regression, random forest, extreme gradient boosting (XGBoost), support vector machine, and neural networks. Model performance was assessed using the area under the receiver operating characteristic (AUC) curve, F1 score, and calibration curves. Clinical decision curve analysis (DCA) was employed to evaluate the clinical utility of the models. SHAP values were used to interpret feature importance in the XGBoost model and enhance its explainability. Results:The XGBoost model demonstrated the best performance in predicting CLBR,with accuracy of 72.44%, AUC of 0.775, and F1 score of 0.654, accuracy and F1 score outperforming logistic regression (accuracy was 70.02%, F1 score was 0.585), random forest (accuracy was 71.69%, F1 score was 0.606), support vector machine (accuracy was 70.20%, F1 score was 0.607), and neural network (accuracy was 68.72%, F1 score was 0.560). The calibration curve of XGBoost closely aligned with the diagonal line, indicating that the predicted probabilities were very close to the actual outcomes, demonstrating good calibration. DCA indicated that the XGBoost model provided higher net benefits across a wide range of clinical decision thresholds. SHAP value analysis identified number of previous IVF failures, antral follicle count, anti-Müllerian hormone level, percentage of normal sperm morphology, and sperm DNA fragmentation index as key predictors of CLBR.Conclusion:The XGBoost model exhibits excellent predictive performance and calibration for CLBR, with SHAP values providing important insights into feature importance. This model has the potential to support the development of personalized treatment strategies in clinical practice. However, its generalizability needs to be validated using external datasets to ensure its applicability to diverse populations.

Objective:To develop and validate machine learning models for predicting the cumulative live birth rate (CLBR) following in vitro fertilization (IVF) and to analyze key predictive features using SHAP values. Methods:This retrospective study included data from patients who underwent IVF-embryo transfer at the Department of Reproductive Medicine, Baoding Maternal and Child Health Hospital, between January 2017 and December 2022. Patients were categorized into two groups based on live birth outcome: the live birth group ( n=1 036) and the non-live birth group ( n=756). The dataset was randomly divided into a training set and a validation set in a ratio of 7∶3. Five algorithms were utilized for model development: logistic regression, random forest, extreme gradient boosting (XGBoost), support vector machine, and neural networks. Model performance was assessed using the area under the receiver operating characteristic (AUC) curve, F1 score, and calibration curves. Clinical decision curve analysis (DCA) was employed to evaluate the clinical utility of the models. SHAP values were used to interpret feature importance in the XGBoost model and enhance its explainability. Results:The XGBoost model demonstrated the best performance in predicting CLBR,with accuracy of 72.44%, AUC of 0.775, and F1 score of 0.654, accuracy and F1 score outperforming logistic regression (accuracy was 70.02%, F1 score was 0.585), random forest (accuracy was 71.69%, F1 score was 0.606), support vector machine (accuracy was 70.20%, F1 score was 0.607), and neural network (accuracy was 68.72%, F1 score was 0.560). The calibration curve of XGBoost closely aligned with the diagonal line, indicating that the predicted probabilities were very close to the actual outcomes, demonstrating good calibration. DCA indicated that the XGBoost model provided higher net benefits across a wide range of clinical decision thresholds. SHAP value analysis identified number of previous IVF failures, antral follicle count, anti-Müllerian hormone level, percentage of normal sperm morphology, and sperm DNA fragmentation index as key predictors of CLBR.Conclusion:The XGBoost model exhibits excellent predictive performance and calibration for CLBR, with SHAP values providing important insights into feature importance. This model has the potential to support the development of personalized treatment strategies in clinical practice. However, its generalizability needs to be validated using external datasets to ensure its applicability to diverse populations.

Objective:To construct novel radiotracers targeting CD36 and evaluate their stabilities and targeting specificities.Methods:ABT-510, an anti-angiogenic peptide that bound CD36, served as the active scaffold for the synthesis of precursor molecules BQ01, BQ02 and BQ03. These precursors were subsequently labeled with 68Ga to yield the tracers 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03, whose radiochemical purities were determined by radio-high-performance liquid chromatography. A systematic characteristics of the radiochemical and biological profiles were performed, including in vitro stability, lipid water partition coefficient (log P), target-binding affinity, pharmacokinetic behaviour, microPET/CT imaging on U87MG tumor bearing mice, biodistribution, and phosphor-screen autoradiography. The tumor/muscle ratios of three probes were compared by one-way analysis of variance (post-hoc tests with Tukey method). Results:The radiochemical purities of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 were all over 95%, and the radiotracers all remained stable in PBS and serum in vitro. The log P values of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 were -3.81±0.08, -3.60±0.03 and -3.85±0.03 respectively, indicating hydrophilicity; and blood clearance half-lives in vivo were (25.6±0.3), (38.2±0.2) and (17.5±0.2) min respectively, demonstrating rapid elimination. 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 displayed high binding affinities toward U87MG cells, with inhibition constants ( Ki) of (4.30±0.63), (3.80±0.24) and (2.61±0.31)nmol/L, respectively. MicroPET/CT demonstrated marked tumor accumulation of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 at 0.5 h after administration in U87MG tumor bearing mice, with SUV max of 0.68±0.09, 0.70±0.09 and 0.89±0.05. Biodistribution results showed the tumor uptakes of 68Ga-BQ01, 68Ga-BQ02 and 68Ga-BQ03 were (0.35±0.09), (0.53±0.01) and (0.63±0.06) percentage activity of injection dose per gram of tissue (%ID/g), respectively. The tumor/muscle ratio of 68Ga-BQ03 was significantly higher than that of 68Ga-BQ01 or 68Ga-BQ02 ( F=161.50, all P<0.001). Conclusions:Three CD36-targeted radiotracers demonstrate good stability, strong binding affinity, and high tumor uptake. Among them, 68Ga-BQ03 shows the best imaging performance and holds promise for the precise diagnosis of CD36-positive malignant tumors.

Objective To establish a high performance liquid chromatographic(HPLC)method for the determination of chidamide in human plasma.Methods The plasma sample was taken as 500 μL,and triamcinolone was used as the internal standard.After liquid-liquid extraction using methyl tert-butyl ether,the supernatant was centrifuged and blown dry under N2,then re-dissolved in 50 μL of water,and then centrifuged again,and then 10 μL of the supernatant was injected into the system.The separation was performed on a Shim-pack CLC-ODS(150 mm×60 mm,5 μm)at 35 ℃ using water-acetonitrile=(74∶26,v/v,adjusted to pH=3 by acetic acid)as mobile phase.The flow rate was 1.0 mL·min-1 and the wavelength was 260 nm.The specificity,standard curve,lower limit of quantitation,precision,recovery and stability of the method were investigated.In addition,the high performance liquid chromatography method described above was applied to determine the plasma drug concentration after oral administration of chidamide in one patient.Results The retention time of chidamide and internal standard was 8.00 and 9.40 min,respectively.The standard curve equation was y=10.28x-0.06(r=0.998).The intra-day and inter-day precision(RSD)of low,medium and high concentration quality control samples(0.02,0.15,0.75 μg·mL-)were 1.00％-4.87％(n=6),and the accuracy was-10.29％-3.37％.The average extraction recovery was 61.74％-69.85％.Conclusion The method was simple,sensitive and accurate,suitable for monitoring the concentrations of chidamide in human plasma.

Objective To analyze the risk factors of gastrointestinal bleeding in patients with type A aortic dissection(TAAD)after Sun's operation.Methods The clinical data of 87 patients who underwent TAAD Sun's operation in our hospital from March 2021 to June 2022 were retrospectively analyzed.They were divided into the bleeding group and the non-bleeding group according to whether there was gastrointestinal bleeding after operation.The clinical data of patients in the two groups was compared and analyzed.The binary Logistic regression analysis was used to analyze the risk factors of gastrointestinal bleeding.The clinical predictor of postoperative gastrointestinal bleeding was analyzed by receiver operating characteristic(ROC)curve.Results In this study,there were 40 cases of postoperative gastrointestinal bleeding(the bleeding group)and 47 cases of non-bleeding(the non-bleeding group).Compared with the non-bleeding group,the bleeding group had a shorter onset time,a higher proportion of patients with hypertension history,a higher preoperative creatinine abnormality rate,more intraoperative blood loss,longer postoperative mechanical ventilation time,higher postoperative infection rate,and higher poor prognosis rate,with statistically significant differences(P<0.05).There was no statistically significant difference in the gender,age,gastrointestinal diseases history,smoking history,preoperative platelets,preoperative international normalized ratio(INR),preoperative alanine aminotransferase(ALT),preoperative aspartate aminotransferase(AST),preoperative γ-glutamyl transpeptidase(GGT),preoperative dissection involving abdominal aorta,operation time,intraoperative cardiopulmonary bypass time,intraoperative circulatory arrest time,intraoperative aortic occlusion time or intraoperative blood transfusion rate.Logistic regression analysis showed that hypertension history(OR=2.468,95%CI:0.862 to 7.067,P=0.037),preoperative creatinine>105 μmol/L(OR=3.970,95%CI:1.352 to 11.659,P=0.011),long postoperative mechanical ventilation time(OR=1.015,95%CI:0.094 to 1.018,P=0.041)and postoperative infection(OR=3.435,95%CI:0.991 to 11.900,P=0.012)were the independent risk factors for postoperative gastrointestinal bleeding in TAAD patients.ROC curve showed that the postoperative mechanical ventilation time exceeding 64 hours were the clinical predictor of postoperative gastrointestinal bleeding in TAAD patients.Conclusion The prognosis of TAAD patients with postoperative gastrointestinal bleeding after Sun's operation is poor.Hypertension history,preoperative acute renal insufficiency,long postoperative mechanical ventilation time and postoperative infection are closely related to postoperative gastrointestinal bleeding in TAAD patients after operation,which should be paid more attention to,and corresponding evaluation,early identification and early intervention should be made to improve the prognosis of patients.

The essential oil from Curcuma longa L. (CLEO) was extracted by steam distillation. In this study, vasorelaxant activity and mechanism of CLEO was explored. Firstly, the experimental results of isolated rat thoracic aorta ring showed that the CLEO had vasorelaxant activity. By removing the endothelium of aorta ring and pre-incubating inhibitor of endothelial nitric oxide synthase (eNOS), it was found that the vasorelaxant activity of CLEO was endothelium-dependent and related to eNOS. By human umbilical vein endothelial cells (HUVECs) model, it was found that the CLEO could promote the production of nitric oxide (NO) in HUVECs, further indicating that the vasorelaxant activity of CLEO was related to eNOS. The results of Western blot showed that CLEO could up-regulate the phosphorylation levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and eNOS. In summary, the CLEO has vasorelaxant activity, and its mechanism is related to activating the endothelial PI3K/Akt/eNOS pathway. All animal experiments in this paper were approved by the Committee of Laboratory Animal Welfare Ethics of Chengdu University of Traditional Chinese Medicine (approval No. 2020-04).