OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment of "biaoben acupoint combination" on cardiomyocyte mitochondrial fission in the rats with myocardial ischemia-reperfusion injury (MIRI) and explore its mechanism. METHODS: Fifty male SD rats were randomly divided into a sham-operation group, a model group, an EA pretreatment group, an EA pretreatment + Compound C group and an EA pretreatment+ML385 group, 10 rats in each group. In the EA pretreatment, the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, EA was delivered at bilateral "Neiguan" (PC6), "Zusanli" (ST36) and "Guanyuan" (CV4) for 20 min, with continuous wave and 2 Hz of frequency, 1 mA of current, once daily for consecutive 7 days. On day 8, in the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, 30 min before model preparation, the intraperitoneal injection with Compound C (0.3 mg/kg) and ML385 (30 mg/kg) was administered respectively. Except in the sham-operation group, the ligation of the left anterior descending coronary artery was performed to prepare MIRI rat model in the rest groups. In the sham-operation group, the thread was not ligated. After modeling, the content of reactive oxygen species (ROS) in the ischemic area was measured by flow cytometry, superoxide dismutase (SOD) was detected using xanthine oxidase method, and malondialdelyde (MDA) was detected using thiobarbituric acid (TBA) chromatometry. The morphology of myocardial tissue in the ischemic area was observed with HE staining, and the mitochondria ultrastructure of cardiomyocytes observed under transmission electron microscopy. Using immunofluorescence analysis, the positive expression of mitochondrial fission factor (MFF), mitochondrial fission 1 protein antibody (Fis1) and dynamin-related protein 1 (Drp1) was detected; and with immunohistochemical method used, the protein expression of adenosine monophosphate-activated protein kinase (AMPK), nuclear factor E2-associated factor2 (Nrf2) and Drp1 in the ischemic area was detected. RESULTS: Compared with the sham-operation group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 increased in the model group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 decreased (P<0.01), and the protein expression of Drp1 elevated (P<0.01). Compared with the model group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01), and the protein expression of Drp1 declined (P<0.01); and in the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the positive expression of MFF, Fis1 and Drp1, and the protein expression of Drp1 were all reduced (P<0.01). When compared with the EA pretreatment + Compound C group and the EA pretreatment+ML385 group, the content of ROS and MDA in the myocardial tissue of the ischemic area, and the positive expression of MFF, Fis1 and Drp1 were dropped in the EA pretreatment group (P<0.01); the content of SOD and the protein expression of AMRK and Nrf2 rose (P<0.01, P<0.05), and the protein expression of Drp1 decreased (P<0.05). In comparison with the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group, the cardiac muscle fiber rupture, cell swelling and mitochondrial disorders were obviously alleviated in the EA pretreatment group. The morphological changes were similar among the model group, the EA pretreatment+Compound C group and the EA pretreatment+ML385 group. CONCLUSION Electroacupuncture pretreatment of "biaoben acupoint combination" attenuates myocardial injury in MIRI rats, probably through promoting the phosphorylation of AMPK and Nrf2, inhibiting the excessive mitochondrial fission induced by Drp1, and reducing mitochondrial dysfunction caused by mitochondrial fragmentation and vacuolation.
Animals ; Electroacupuncture ; Male ; Rats, Sprague-Dawley ; Myocardial Reperfusion Injury/physiopathology* ; Myocytes, Cardiac/cytology* ; Rats ; Acupuncture Points ; Mitochondrial Dynamics ; Humans ; Reactive Oxygen Species/metabolism* ; NF-E2-Related Factor 2/genetics* ; Superoxide Dismutase/metabolism*

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

ObjectiveTo establish fingerprint profiles and a quantitative determination method for Lycii Cortex， providing a scientific basis for the formulation of quality standards for Lycii Cortex and its roasted products. MethodsHigh performance liquid chromatography（HPLC） was developed for the quantitative method for determining kukoamine B in Lycii Cortex and its roasted products on an Alphasil XD-C₁₈ CH column（4.6 mm×250 mm， 5 μm）. HPLC fingerprint profiles were established for 10 batches of Lycii Cortex and its roasted products， and ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to identify the common peaks based on reference standards， literature and MS information. Quality evaluation indicators included yield of decoction pieces， appearance properties， content of kukoamine B， and fingerprint profiles. The temperature and time of the roasting process were investigated to select the optimal preparation process， which was then verified. Additionally， chemical pattern recognition was combined to assess the differences in the chemical composition of Lycii Cortex before and after roasting， as well as among samples from different origins. ResultsQuantitative analysis indicated that the contents of kukoamine B in Lycii Cortex and its roasted products were 0.35%-5.51% and 0.24%-4.15%， respectively. The transfer rate of kukoamine B was 58.6%-78.9% after roasting. The fingerprint profile analysis demonstrated that the method established in this study effectively separated kukoamine B from other components in the samples and distinctly differentiated it from its impurity peak， cis-N-caffeoylputrescine. The HPLC fingerprint profiles of Lycii Cortex and its roasted products showed high similarity（all above 0.95）， with 7 common peaks identified and five common components， including kukoamine B， cis-N-caffeoylputrescine， N-coumaroyl tyramine， feruloyltyramine， and glucosyringic acid， confirmed. Process optimization confirmed that baking at 110 ℃ for 20 min was a stable and feasible method for roasting Lycii Cortex. Principal component analysis and cluster analysis showed that there was little difference in the chemical composition between raw and roasted Lycii Cortex， but the quality of Lycii Cortex from different origins differed greatly. ConclusionThis study successfully established the fingerprint profiles and a quantitative method for the effective component kukoamine B in Lycii Cortex and roasted Lycii Cortex. The qualitative and quantitative analyses clarified that the impact of the roasting process on the chemical composition of Lycii Cortex was less significant than the variations due to its geographical origin. The findings of this study offer a reference for the development of quality evaluation methods and the establishment of quality standards for Lycii Cortex and its processed products.

Objective: To explore the plasma metabonomic characteristics of patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome. Methods: One hundred and three patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome were enrolled from November 2023 to February 2024 in the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and 54 healthy individuals were recruited. The general data of the two groups were analyzed, and the plasma metabolite content was detected using ultra-high performance liquid chromatography-Orbitrap mass spectrometry. Construct an orthogonal partial least squares discriminant analysis model to screen metabolites with significant intergroup changes. The variable importance in projection≥ 1, |log2FC|>1, and P<0.05 were used as the criteria for the screening of differential metabolites. Annotate differential metabolites using internal databases and the human metabolome database, and perform pathway analysis using MetaboAnalyst website. Results: There was no statistically significant difference in gender and age between the two groups.Seventeen potential differential metabolites were identified. The D-4′-phosphopantothenate, 2, 6-dichloroindophenol, 4-methylphenol, hypoxanthine, 11, 12-epoxyeicosatrienoic acids, oleamide, 3-phenyllactic acid contents were higher in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05); 3-anisic acid, 3-iodo-octadecanoic acid, mebendazole, β-alanine, citric acid, trans-aconitic acid, geranyl diphosphate, lysophosphatidylcholine(18∶2), phosphatidylethanolamine(18∶1), and caprolactam contents were lower in patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome than in healthy individuals(P<0.05). Ten metabolic pathways were identified, including the key metabolic pantothenate and coenzyme A biosynthesis pathways. Conclusion Metabolic differences were observed between patients with type 2 diabetes mellitus and turbid toxin accumulation syndrome and healthy individuals, and the underlying mechanism may involve the pantothenate and coenzyme A biosynthesis pathways, jointly mediated by D-4′-phosphopantothenate and β-alanine.

Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49％,8.71％,10.86％and 14.85％,respectively(Log-rank P＜0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95％CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03～1.24),1.18(1.07～1.29),1.22(1.12～1.34),respectively;the HR(95％CI)of myocardial infarction were 1.15(0.87～1.53),1.44(1.10～1.88),1.67(1.29～2.17),respectively;the HR(95％CI)of revascularization were 1.21(0.99～1.49),1.31(1.07～1.60)and 1.49(1.22～1.81),respectively;the HR(95％CI)of ischemic stroke were 1.17(1.03～1.32),1.17(1.04～1.33)and 1.21(1.06～1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.

Objective:To investigate the association of Chinese visceral adiposity index (CVAI) with arterial stiffness progression.Methods:This study was a prospective cohort study, which included participants who completed at least 1 measurement of brachial-ankle pulse wave velocity (baPWV) between 2010 and 2016, with complete physical examination data during the same period, and completed baPWV measurement during follow-up. The time of completing the first baPWV measurement was defined as the baseline. All participants were divided into 4 groups according to quartiles of baseline CVAI (<60.84, 60.84-89.67, 89.68-117.45,≥117.46). The baPWV progression was calculated (baPWV progression=(baPWV follow-up-baPWV baseline)/duration of follow-up). We assessed the association of CVAI groups with baPWV progression using multivariate linear regression models. Results:A total of 17 261 participants were included. Of these, the age was (47.6±11.6) years, and 11 285 (65.38%) were males. The results of multivariate linear regression models showed that compared with the CVAI<60.84 group, the baPWV at baseline increased by 39.62 cm/s (95% CI 28.57-50.67, P<0.01) in the 60.84-89.67 group, 76.37 cm/s (95% CI 64.71-88.04, P<0.01) in the 89.68-117.45 group, and 92.83 cm/s (95% CI 80.53-105.14, P<0.01) in the≥117.46 group. The median follow-up time was 2.49 years. Compared with the CVAI<60.84 group, annual change of baPWV progression increased by 17.17 cm/s (95% CI 10.36-23.97, P<0.01) in the 60.84-89.67 group, 24.59 cm/s (95% CI 17.38-31.80, P<0.01) in the 89.68-117.45 group, and 25.75 cm/s (95% CI 18.13-33.36, P<0.01) in the ≥117.46 group. Conclusion:Higher CVAI is closely associated with the progression of arterial stiffness, and the arterial stiffness progression accelerates with increased CVAI.

Objective The aim of this study was to analysis the incidence and mortality of malignant tumors in the cancer registration area of Kunming City in 2020,as well as the trend of changes from 2016 to 2020.Methods The malignant tumor data of 12 cancer registration areas in Kunming in 2020 that met the quality criteria were used to analyze the crude incidence,crude mortali-ty,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)of malignant tumors in different gen-ders and regions.The annual percentage change(APC)was calculated using Joinpoint 5.3.0.0 software,the incidence and mortality trends of malignant tumors from 2016 to 2020 were evaluated.Results In 2020,the crude incidence and ASIRC of malignant tumors in cancer registration areas of Kunming City were 234.27/100,000 and 141.68/100,000,respectively.The ASIRC of males was high-er than that of females(146.94/100,000 vs.137.33/100,000,Z=3.459,P<0.001),and that of rural areas was higher than that of urban areas(146.37/100,000 vs.134.09/100,000,Z=-4.462,P<0.001).The crude mortality and ASMRC of malignant tumors were 135.67/100,000 and 73.18/100,000,respectively.The ASMRC of males was higher than that of females(91.65/100,000 vs.55.43/100,000,Z=19.260,P<0.001),and that of rural areas was higher than that of urban areas(76.27/100,000 vs.70.00/100,000,Z=-3.359,P<0.001).There were 81.39%of new cases and 90.36%of deaths of malignant tumors occurred in the popu-lation aged 50 and above.The top 5 cancer incidence in the Kunming City were lung cancer,colorectal cancer,breast cancer,liver cancer and prostate cancer.The top 5 cancer mortality were lung cancer,liver cancer,colorectal cancer,prostate cancer and stomach cancer.The ASIRC(APC=-3.05%,95%CI:-5.91%--0.10%,P=0.046)and ASMRC(APC=-5.47%,95%CI:-8.52%--2.32%,P=0.012)of malignant tumors in urban areas of Kunming showed a downward trend.Conclusions From 2016 to 2020,the ASIRC and ASMRC of malignant tumors in urban areas of Kunming showed a downward trend,but there was no significant changing trend in rural tumor registration areas.Rural areas are key areas for the prevention and treatment of malignant tumors in Kunming city;Lung cancer,colorectum cancer,liver cancer and prostate cancer are the key types of cancer for prevention and treatment.

Aim To investigate the effect of cumulative non-high density lipoprotein cholesterol/high density lip-oprotein cholesterol(non-HDLC/HDLC)exposure on atherosclerotic cardiovascular disease(ASCVD).Methods A prospective cohort study was conducted.A total of 50 777 employees of Kailuan Group who participated in three physical examinations in 2006-2007,2008-2009 and 2010-2011 were selected as the study subjects.Groups were divided into Q1,Q2,Q3 and Q4 according to the cumulative non-HDLC/HDLC exposure quartiles.Kaplan-Meier curve was used to calculate the cumulative incidence of ASCVD in different cumulative non-HDLC/HDLC groups,and Log-rank test was used to compare the differences among groups.Cox proportional risk model was used to analyze the effect of cumulative non-HDLC/HDLC exposure on ASCVD.Results The average follow-up was(10.19±2.21)years,and 5 003 new cases of ASCVD occurred.The cumulative incidence of ASCVD in groups Q1 to Q4 was 6.49％,8.71％,10.86％and 14.85％,respectively(Log-rank P＜0.01).Multivariate Cox regression analysis showed that compared with group Q1,the HR(95％CI)of ASCVD in groups Q2,Q3 and Q4 were 1.13(1.03～1.24),1.18(1.07～1.29),1.22(1.12～1.34),respectively;the HR(95％CI)of myocardial infarction were 1.15(0.87～1.53),1.44(1.10～1.88),1.67(1.29～2.17),respectively;the HR(95％CI)of revascularization were 1.21(0.99～1.49),1.31(1.07～1.60)and 1.49(1.22～1.81),respectively;the HR(95％CI)of ischemic stroke were 1.17(1.03～1.32),1.17(1.04～1.33)and 1.21(1.06～1.37),respectively;but the above association was not found when heart failure and atrial fibrillation were used as the outcome events.The restricted cubic spline showed that cumulative non-HDLC/HDLC values were line-arly associated with the risk of ASCVD.Conclusion Cumulative non-HDLC/HDLC exposure was positively associated with the risk of ASCVD.

Objective The aim of this study was to analysis the incidence and mortality of malignant tumors in the cancer registration area of Kunming City in 2020,as well as the trend of changes from 2016 to 2020.Methods The malignant tumor data of 12 cancer registration areas in Kunming in 2020 that met the quality criteria were used to analyze the crude incidence,crude mortali-ty,age-standardized incidence/mortality rate by Chinese standard population(ASIRC/ASMRC)of malignant tumors in different gen-ders and regions.The annual percentage change(APC)was calculated using Joinpoint 5.3.0.0 software,the incidence and mortality trends of malignant tumors from 2016 to 2020 were evaluated.Results In 2020,the crude incidence and ASIRC of malignant tumors in cancer registration areas of Kunming City were 234.27/100,000 and 141.68/100,000,respectively.The ASIRC of males was high-er than that of females(146.94/100,000 vs.137.33/100,000,Z=3.459,P<0.001),and that of rural areas was higher than that of urban areas(146.37/100,000 vs.134.09/100,000,Z=-4.462,P<0.001).The crude mortality and ASMRC of malignant tumors were 135.67/100,000 and 73.18/100,000,respectively.The ASMRC of males was higher than that of females(91.65/100,000 vs.55.43/100,000,Z=19.260,P<0.001),and that of rural areas was higher than that of urban areas(76.27/100,000 vs.70.00/100,000,Z=-3.359,P<0.001).There were 81.39%of new cases and 90.36%of deaths of malignant tumors occurred in the popu-lation aged 50 and above.The top 5 cancer incidence in the Kunming City were lung cancer,colorectal cancer,breast cancer,liver cancer and prostate cancer.The top 5 cancer mortality were lung cancer,liver cancer,colorectal cancer,prostate cancer and stomach cancer.The ASIRC(APC=-3.05%,95%CI:-5.91%--0.10%,P=0.046)and ASMRC(APC=-5.47%,95%CI:-8.52%--2.32%,P=0.012)of malignant tumors in urban areas of Kunming showed a downward trend.Conclusions From 2016 to 2020,the ASIRC and ASMRC of malignant tumors in urban areas of Kunming showed a downward trend,but there was no significant changing trend in rural tumor registration areas.Rural areas are key areas for the prevention and treatment of malignant tumors in Kunming city;Lung cancer,colorectum cancer,liver cancer and prostate cancer are the key types of cancer for prevention and treatment.

Objective:To investigate the association of Chinese visceral adiposity index (CVAI) with arterial stiffness progression.Methods:This study was a prospective cohort study, which included participants who completed at least 1 measurement of brachial-ankle pulse wave velocity (baPWV) between 2010 and 2016, with complete physical examination data during the same period, and completed baPWV measurement during follow-up. The time of completing the first baPWV measurement was defined as the baseline. All participants were divided into 4 groups according to quartiles of baseline CVAI (<60.84, 60.84-89.67, 89.68-117.45,≥117.46). The baPWV progression was calculated (baPWV progression=(baPWV follow-up-baPWV baseline)/duration of follow-up). We assessed the association of CVAI groups with baPWV progression using multivariate linear regression models. Results:A total of 17 261 participants were included. Of these, the age was (47.6±11.6) years, and 11 285 (65.38%) were males. The results of multivariate linear regression models showed that compared with the CVAI<60.84 group, the baPWV at baseline increased by 39.62 cm/s (95% CI 28.57-50.67, P<0.01) in the 60.84-89.67 group, 76.37 cm/s (95% CI 64.71-88.04, P<0.01) in the 89.68-117.45 group, and 92.83 cm/s (95% CI 80.53-105.14, P<0.01) in the≥117.46 group. The median follow-up time was 2.49 years. Compared with the CVAI<60.84 group, annual change of baPWV progression increased by 17.17 cm/s (95% CI 10.36-23.97, P<0.01) in the 60.84-89.67 group, 24.59 cm/s (95% CI 17.38-31.80, P<0.01) in the 89.68-117.45 group, and 25.75 cm/s (95% CI 18.13-33.36, P<0.01) in the ≥117.46 group. Conclusion:Higher CVAI is closely associated with the progression of arterial stiffness, and the arterial stiffness progression accelerates with increased CVAI.