ObjectiveTo explore the vascular endothelial injury in male mice caused by exposure to polystyrene microplastics （PS-MPs） and the intervention effect of luteolin on vascular remodeling. Additionally， to investigate the mechanism through the oxidative system and metabolomics. MethodsThirty-two C57BL/6 mice （6-8 weeks old） were randomly divided into the saline group （saline group）， the 0.1 mg/kg PS-MPs exposure group （0.1PS-MPs group）， the 1 mg/kg PS-MPs exposure group （1PS-MPs group）， and the 1 mg/kg PS-MPs + luteolin treatment group （1PS-MPs + Lut group）， with 8 mice in each group. After 8 weeks of intervention， the body weight， blood pressure， aortic organ coefficient， and aortic histopathological changes of mice in each group were detected； the total cholesterol （TC）， triglyceride （TG）， and high-density lipoprotein cholesterol （HDL-C） lipid metabolism-related indicators in the aorta of mice were detected； the reactive oxygen species （ROS）， glutathione （GSH）， and malondialdehyde （MDA） oxidative stress-related indicators were detected； the endothelin （ET-1）， nitric oxide （NO）， vascular endothelial growth factor A （VEGF-A）， vascular cell adhesion molecule-1 （VCAM-1/CD106）， and intercellular adhesion molecule-1 （ICAM-1/CD54） endothelial function-related indicators and serum metabolomics were detected. ResultsCompared to the saline group， exposure to PS-MPs resulted in pathological thickening of the mouse aorta， increased aortic organ coefficient， and elevated blood pressure. Lipid metabolism-related indicators， including TC and TG， were elevated， while HDL-C was reduced， indicating lipid metabolism disorder in mice. Oxidative stress markers such as ROS and MDA increased， whereas GSH decreased， demonstrating oxidative damage. Vascular endothelial inflammation and injury markers， including ET-1， VEGF-A， VCAM-1， and ICAM-1， were upregulated， while the vasodilatory substance NO was downregulated， confirming endothelial injury. Furthermore， serum metabolomics results revealed that PS-MPs exposure induced endothelial damage by disrupting metabolic pathways such as the citrate cycle. Compared to the PS-MPs group， luteolin significantly reversed these effects， attenuating oxidative stress and lipid metabolism disorders， and effectively repairing endothelial injury. ConclusionPS-MPs induce vascular toxicity through oxidative stress and lipid metabolism. Luteolin effectively alleviates endothelial damage and vascular remodeling.

Aim To investigate the effect of dihydro-myricetin(DMY)on Ang Ⅱ-induced cardiac hypertro-phy in mice and the underlying mechanisms.Methods Fifty mice were randomly divided into control group,Ang Ⅱ group,Ang Ⅱ+catopril 12.0 mg·kg-1·d-1 group,AngⅡ+DMY 100 mg·kg-1·d-1 group,and Ang Ⅱ+DMY 200 mg·kg-1·d-1 group,with 10 mice in each group.The control mice were given saline by gavage,the drug intervention group was given DMY,and the positive drug group was given captopril;the mice in all groups except the control group were in-jected subcutaneously with Ang Ⅱ 1.0mg·kg-1·d-1.After four weeks,heart weight/body weight(HW/BW)and left ventricular weight/body weight(LVW/BW)ratios were calculated.The mRNA ex-pression of the fetal genes atrial natriuretic factor(ANF),brain natriuretic peptide(BNP),β-myosin heavy chain(β-MHC),adenosine triphosphate 5β-subunit(ATP 5β)and uncoupling protein 2(UCP2)were monitored,and the morphological changes of car-diac tissue were observed.Secondly,the creatine ki-nase isoenzyme(CK-MB),lactate dehydrogenase(LDH),free fatty acids(FFA)and lactic acid in ser-um were investigated.Lastly,the expression of AMP-activated proteinkinase(AMPK),peroxisome prolifer-ator-activated receptor alpha(PPAR-α)and T-cell nu-clear factor cytoplasmic 4(NFATc4)protein expres-sion were also detected.The Ang Ⅱ-induced H9C2 cardiomyocyte hypertrophy model was established and treated with the AMPK inhibitor compound C.The mRNA of ANF,BNP,β-MHC and the protein expres-sion of AMPK/PPAR-α were analyzed.Results DMY intervention significantly reduced HW/BW and LVW/BW in mice,fetal genes ANF,BNP,β-MHC and UCP2 mRNA expression decreased,whereas ATP 5 β mRNA increased,and the degree of hypertrophy of cardiomyocytes was alleviated.In addition,the serum levels of CK-MB,LDH,FFA and lactic acid were re-duced in DMY treated groups.Finally,DMY upregu-lated the protein expression of P-AMPK,AMPK and PPAR-α,and downregulated protein expression of NFATc4.In the Ang Ⅱ-induced cardiomyocyte hyper-trophy model,DMY pretreatment reduced the mRNA expression of fetal genes(ANF,BNP,β-MHC).However,when AMPK was inhibited by compound C,the expression of these fetal genes rebounded,accom-panied by decreased protein levels of AMPK and PPAR-α.Conclusions DMY can improve Ang Ⅱ-in-duced myocardial hypertrophy in mice by ameliorating disorders of glycolipid metabolism and increasing ener-gy supply to cardiomyocytes,and its mechanism is re-lated to the activation of the AMPK/PPAR-α pathway and the inhibition of NFATc4 expression.

Aim To explore the mechanism of Jiawei Shaofu Zhuyu decoction in antagonizing endometriosis fibrosis by regulating mitophagy.Methods After the animal model was constructed,the syndrome was evalu-ated by general condition,organ water content and ther-mal imaging.The curative effect was evaluated by the weight of ectopic focus and the degree of adhesion.The pathological changes were compared using HE stai-ning,transmission electron microscopy,Masson and Sir-ius red staining.The expression of PINK1 and Parkin was detected by immunohistochemistry.The expression of mRNA and protein was determined by qPCR and Western blot,and the level of serum ROS was detected by ELISA.Results The autonomic activity of model mice was weakened,the water content of organs rose,and the temperature of limbs and lower abdomen was reduced by thermal imaging.HE staining showed obvi-ous hyperplasia of ectopic epithelium and glands.Transmission electron microscopy showed mitochondrial and endoplasmic reticulum structure damage,and nor-mal autophagy structure disappeared.Masson and Siri-us red staining showed increased collagen deposition;immunohistochemistry showed decreased expression of PINK1 and Parkin in ectopic foci.qPCR and Western blot showed that the expression of PINK1,Parkin,Bec-lin1,LC3 mRNA and protein in ectopic foci of model mice decreased,the expression of p62 mRNA and pro-tein increased,and serum ROS increased.The syn-drome performance of model mice was improved after the intervention of Jiawei Shaofu Zhuyu decoction;the inflammatory infiltration of ectopic foci was relieved,the morphology of mitochondria and endoplasmic retic-ulum was restored,and normal autophagy structure ap-peared.The degree of collagen deposition and fibrosis was reduced;the mRNA and protein expression of PINK1,Parkin,Beclin1 and LC3 increased.The ex-pression of p62 mRNA and protein decreased,and the level of ROS decreased.Conclusions Jiawei Shaofu Zhuyu decoction can improve the fibrosis of ectopic le-sions in mice with endometriosis of cold-dampness sta-sis syndrome,which may be related to the regulation of mitophagy.

Aim To investigate the effect of dihydro-myricetin(DMY)on Ang Ⅱ-induced cardiac hypertro-phy in mice and the underlying mechanisms.Methods Fifty mice were randomly divided into control group,Ang Ⅱ group,Ang Ⅱ+catopril 12.0 mg·kg-1·d-1 group,AngⅡ+DMY 100 mg·kg-1·d-1 group,and Ang Ⅱ+DMY 200 mg·kg-1·d-1 group,with 10 mice in each group.The control mice were given saline by gavage,the drug intervention group was given DMY,and the positive drug group was given captopril;the mice in all groups except the control group were in-jected subcutaneously with Ang Ⅱ 1.0mg·kg-1·d-1.After four weeks,heart weight/body weight(HW/BW)and left ventricular weight/body weight(LVW/BW)ratios were calculated.The mRNA ex-pression of the fetal genes atrial natriuretic factor(ANF),brain natriuretic peptide(BNP),β-myosin heavy chain(β-MHC),adenosine triphosphate 5β-subunit(ATP 5β)and uncoupling protein 2(UCP2)were monitored,and the morphological changes of car-diac tissue were observed.Secondly,the creatine ki-nase isoenzyme(CK-MB),lactate dehydrogenase(LDH),free fatty acids(FFA)and lactic acid in ser-um were investigated.Lastly,the expression of AMP-activated proteinkinase(AMPK),peroxisome prolifer-ator-activated receptor alpha(PPAR-α)and T-cell nu-clear factor cytoplasmic 4(NFATc4)protein expres-sion were also detected.The Ang Ⅱ-induced H9C2 cardiomyocyte hypertrophy model was established and treated with the AMPK inhibitor compound C.The mRNA of ANF,BNP,β-MHC and the protein expres-sion of AMPK/PPAR-α were analyzed.Results DMY intervention significantly reduced HW/BW and LVW/BW in mice,fetal genes ANF,BNP,β-MHC and UCP2 mRNA expression decreased,whereas ATP 5 β mRNA increased,and the degree of hypertrophy of cardiomyocytes was alleviated.In addition,the serum levels of CK-MB,LDH,FFA and lactic acid were re-duced in DMY treated groups.Finally,DMY upregu-lated the protein expression of P-AMPK,AMPK and PPAR-α,and downregulated protein expression of NFATc4.In the Ang Ⅱ-induced cardiomyocyte hyper-trophy model,DMY pretreatment reduced the mRNA expression of fetal genes(ANF,BNP,β-MHC).However,when AMPK was inhibited by compound C,the expression of these fetal genes rebounded,accom-panied by decreased protein levels of AMPK and PPAR-α.Conclusions DMY can improve Ang Ⅱ-in-duced myocardial hypertrophy in mice by ameliorating disorders of glycolipid metabolism and increasing ener-gy supply to cardiomyocytes,and its mechanism is re-lated to the activation of the AMPK/PPAR-α pathway and the inhibition of NFATc4 expression.

This paper uses literature and network data to systematically sort out the theoretical and practical foundations of global public health cooperation,combines expert interviews to conduct empirical analyses,and further explores China's strategies for participating in global public health cooperation through quantitative statistics and text mining of interview data,and proposes a plan for China's participation in global public health cooperation under the current international situation.Under the countercurrents to globalization,China should take its own public health capacity building as the foundation,put global security and health equity at the core,with a philosophy of open cooperation and sustainable development,actively promote bilateral and multilateral cooperation,focus on cultivating global health talents,and enhance the effectiveness of disease prevention and control by making use of existing platforms,international mechanisms and digital health technologies,so as to help build a Global Community of Health for All.

Objective:To explore the factors associated with the efficacy of high-frequency repetitive transcranial magnetic stimulation (rTMS) in the treatment of neuropathic pain (NP) following spinal cord injury (SCI).Methods:This was a retrospective study of 89 SCI survivors with NP receiving high-frequency rTMS. Those with a ≥30% reduction in their Numeric Rating Scales (NRS) scores after 2 weeks of treatment were termed Responders ( n=36), with the others classified as non-responders ( n=53). Demographic data (gender, education level, age), SCI characteristics (injury etiology, injury severity, neurological injury level, injury duration), NP characteristics (pain type, pain intensity, analgesic use), functional assessment (Modified Ashworth Scale score, Spinal Cord Independence Measure score, Modified Barthel Index score, American Spinal Injury Association motor/sensory score) were collected. Least absolute shrinkage and selection operator (LASSO) regression was used for variable selection, followed by binary logistic regression to identify factors associated with treatment efficacy. Results:Among the 89 patients, 36 (40.4%) were Responders to high-frequency rTMS. Binary logistic regression revealed that those with a cervical spinal cord injury and/or spasticity and women were more likely to respond to high-frequency rTMS.Conclusions:Female gender, cervical spinal cord injury, and spasticity are independent factors predicting rTMS efficacy in treating SCI, with spasticity demonstrating the strongest association.

Objective:To perform RHD gene detection on a blood sample with serological weak D phenotype.Methods:A specimen received by the People's Hospital of Zhijin County was serologically identified by the microcolumn gel method and saline method.RHD gene detection was conducted by the PCR-SSP method,and the full sequence determination of the 10 exons amplified was performed.The sequencing results were compared with the ISBT database to determine the genotype.Bioinformatics tool was used to predict the functional damage of mutant proteins,and Alphafold-3 was used for tertiary structural modeling of wild-type and mutant RhD proteins,and the structures of the two proteins were compared and analyzed to explore the reasons why mutations lead to weak serological manifestations.Results:The patient's genotype was identified as RHD*DV.5/RHD*01N.01 heterozygote,with the complete deletion of RHD genes on one chromosome,unable to express the D antigen.On the other chromosome,a G＞A mutation occurred at the 697th base of the 5th exon,resulting in a partial D phenotype.This mutation causes internal hydrogen bond changes at the 233 position of RhD protein,resulting in a change in the conformation of the protein,affecting binding to the corresponding antibody.Conclusion:The patient is a heterozygous mutant individual with RHD*DV.5/RHD*01N.01,exhibiting a partial D phenotype serologically.This variation is extremely rare and has been scarcely reported globally.

Objective To investigate the association of endometrial thickness(EMT)with obstetric and neonatal outcomes of monoparous pregnancy in fresh cleavage embryos transfer.Methods A total of 1 845 patients of monoparous pregnancy after fresh cleavage embryos transfer cycles from Jan 2016 to Mar 2022 at Shanghai First Maternity and Infant Hospital,Tongji Universtiy were analyzed retrospectively.Patients were categorized into three groups by EMT on transferation day:≤8 mm(group A),8-14 mm(group B)and≥14 mm(group C).The primary outcomes were preterm birth(PTB),birth weight and birth weight z-score,small-for-gestation age,large-for-gestation age,very low birth weight,low birth weight and macrosomia.The second outcomes were pregnancy and perinatal complications.The relationship between EMT and adverse neonatal outcomes was estimated by Logistic regression analysis.Results The rate of ectopic pregnancy was increased significantly in group A.No significant differences were found among the three groups in gestation age,birth weight,birth weight z-score,PTB,small for gestation age,large for gestation age,low birth weight,very low birth weight and macrosomia.Compared with group B,the odds of adverse neonatal outcomes did not show significant differences before and after adjustment in both group A and group C by Logistic regression analysis.Conclusion Thinner EMT in fresh cleavage embryos transfer is associated with higher rate of ectopic pregnancy,while it is not independently associated with adverse perinatal outcomes.

Objective:To perform RHD gene detection on a blood sample with serological weak D phenotype.Methods:A specimen received by the People's Hospital of Zhijin County was serologically identified by the microcolumn gel method and saline method.RHD gene detection was conducted by the PCR-SSP method,and the full sequence determination of the 10 exons amplified was performed.The sequencing results were compared with the ISBT database to determine the genotype.Bioinformatics tool was used to predict the functional damage of mutant proteins,and Alphafold-3 was used for tertiary structural modeling of wild-type and mutant RhD proteins,and the structures of the two proteins were compared and analyzed to explore the reasons why mutations lead to weak serological manifestations.Results:The patient's genotype was identified as RHD*DV.5/RHD*01N.01 heterozygote,with the complete deletion of RHD genes on one chromosome,unable to express the D antigen.On the other chromosome,a G＞A mutation occurred at the 697th base of the 5th exon,resulting in a partial D phenotype.This mutation causes internal hydrogen bond changes at the 233 position of RhD protein,resulting in a change in the conformation of the protein,affecting binding to the corresponding antibody.Conclusion:The patient is a heterozygous mutant individual with RHD*DV.5/RHD*01N.01,exhibiting a partial D phenotype serologically.This variation is extremely rare and has been scarcely reported globally.

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.