ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

Objective:To explore the spatial correlation between gray matter volume (GMV) changes and neurotransmitter receptors/transporters in patients with first-episode schizophrenia (FES) .Methods:Fifty-four FES patients(FES group) and fifty-nine healthy controls (HC group) were selected from June 2014 to May 2020 in the Psychiatry Department of Renmin Hospital of Wuhan University. Structural magnetic resonance imaging (sMRI) was conducted on all subjects. Differences of GMV were compared across 400 cortical regions and 32 subcortical regions. Based on the positron emission tomography(PET) data from Neuromaps, which provides the density of 19 different neurotransmitter receptors and transporters, Spearman correlation analysis was performed to evaluate the spatial correlation between GMV changes and neurotransmitter systems.Results:Compared to the HC group, FES group exhibited significant GMV reductions in widespread cortical (90/400) and subcortical (6/32) regions (all FDR-corrected P<0.05). The effect size of GMV reduction (Cohen’s d) showed significant positive correlations with the density of 5-hydroxytryptamine 1a(5HT1a) ( r=0.400, Pspin=0.002), γ-aminobutyric acid type A receptor(GABA A)( r=0.307, Pspin=0.002), and metabotropic glutamate receptor 5(mGluR5) ( r=0.275, Pspin=0.020) receptors (all FDR-corrected P<0.05). Conclusion:GMV reductions in a wide range of brain regions existed in patients with FES. There are significant correlations between 5HT1a, GABA A and mGluR5 receptors and gray matter reduction in patients with FES. The disorder of these neurotransmitter receptors may be the potential neurobiological mechanism of gray matter structural abnormalities in the early stage of schizophrenia.

BACKGROUND:With the popularization of implant technology,the incidence of peri-implantitis is increasing year by year,but the etiological mechanism is still unclear.Highly plastic macrophages can be polarized into M1 and M2 types under microenvironment stimulation,which play pro-inflammatory and anti-inflammatory effects,respectively,and play an important role in host defense,immune response,and maintenance of internal environment homeostasis in peri-implant tissues.The polarization trend of M1/M2 macrophages is closely related to the balance of foreign body response around implants.OBJECTIVE:Lipopolysaccharide and titanium particles are important pathogenic factors causing peri-implantitis,in order to further explore their inducible effect on macrophage polarization in peri-implant tissues.METHODS:The Chinese keywords were"peri-implantitis,macrophage polarization,lipopolysaccharide,titanium particles."The English keywords were"macrophage polarization,peri-implant inflammation,peri-implantitis,LPS,TLRs,NF-κB."The CNKI and PubMed databases were searched,and the relevant literature was screened and sorted to analyze the induction effect and related mechanism of lipopolysaccharide and titanium particles on M1/M2 polarization of macrophages in peri-implant tissues.RESULTS AND CONCLUSION:(1)Lipopolysaccharide and titanium particles may induce macrophage polarization in peri-implant tissues through Toll-like receptor/nuclear factor κB and other related signaling pathways,causing M1/M2 polarization imbalance and thus affecting the occurrence and progression of peri-implantitis.Some drugs can also regulate macrophage M1/M2 polarization through Toll-like receptor/nuclear factor κB signaling pathway to treat related inflammatory diseases.(2)By analyzing the induction effect of lipopolysaccharide and titanium particles on macrophage M1/M2 polarization in peri-implant tissues,the mechanism of their regulation of Toll-like receptor/nuclear factor κB signaling pathway to induce macrophage polarization is further explained,in order to provide some new ideas and strategies for the study of immune prevention and treatment of peri-implantitis.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objective To explore the short-term efficacy and safety of AngioJet mechanical thrombus removal,large lumen cathe-ter thrombus aspiration,and simple catheter-directed thrombolysis(CDT)for the treatment of acute deep venous thrombosis(DVT)of lower extremity.Methods A total of 75 patients with acute lower extremity DVT received interventional therapy were analyzed retrospectively,including 22 patients in AngioJet mechanical thrombus removal(group A),32 patients in large lumen catheter thrombus aspiration(group B),and 21 patients in simple CDT(group C).The short-term efficacy,health economics index,laboratory index and complications of the three groups were compared.Results The success rate of the three groups was 100％.Group A had superior thrombus clearance rates,lower dosages of urokinase,shorter thrombolysis durations,and shorter hospital stays compared to groups B and C.However,the hospitalization costs in group A were significantly higher than those in groups B and C,with statistically significant differences(P＜0.05).No significant renal dysfunction and severe complications were observed in the three groups.Post-operative creatinine levels in group A were higher than those in groups B and C,with statistically significant differences(P＜0.05).Both groups A and B experienced significant decreases in hematocrit postoperatively,and the absolute decrease and percentage decrease in hematocrit in group A were significantly greater than those in group C,with statistically significant differences(P＜0.05).Conclusion Compared to large lumen catheter thrombus aspiration and simple CDT treatment,AngioJet mechanical thrombus removal demonstrates higher efficiency in thrombus clearance rate but is associated with higher costs and risks of renal dysfunction.Postoperative care should focus on protecting renal function.

With the deepening understanding of the pathogenesis of membranous nephropathy(MN),novel targeted drugs,including those targeting B cells,plasma cells,and the complement system,have provided new treatment options for MN,especially for refractory membranous nephropathy(RMN).These novel targeted drugs precisely act on key pathological components such as B cells,plasma cells,and the complement system,demonstrating significant efficacy with minimal adverse effects.This review systematically summarizes the clinical research progress of drugs such as anti-CD20 monoclonal antibodies,anti-B cell activating factor monoclonal antibodies,and anti-CD38 monoclonal antibodies in the treatment of MN and RMN,analyzing the mechanisms by which these novel targeted drugs precisely regulate immune responses to enhance clinical outcomes.It emphasizes the importance of individualized treatment strategies based on the pathogenesis and disease state,explores the potential of combination therapies,and aims to provide new insights for the precise treatment of MN and RMN.

Objective To systematically analyze international and domestic policy frameworks regarding college students'physical activity and the psychological and behavioral health,and to explore representative theoretical models of how physical activity promoting psychological and behavioral health.Methods Thematic analysis and theoretical research methods were employed to examine WHO's Global Action Plan on Physical Activity 2018-2030:More Active People for a Healthier World,EU's Health-enhancing Physical Activity(HEPA)Policy Audit Tool(PAT):version 2,American College of Sports Medicine's Guidelines for Exercise Test-ing and Prescription,Canadian 24-Hour Movement Guidelines for Children and Youth,and China's Opinions on Strengthening School Sports to Promote the Comprehensive Development of Students'Physical and Mental Health,Guidelines for Mental Health Education in Higher Education Institutions,Healthy China Initiative(2019-2030)and Special Action Plan for Comprehensively Strengthening and Improving Student Mental Health Work in the New Era(2023-2025).Four theoretical models were analyzed including self-determination theory(SDT),the-ory of planned behavior(TPB),broaden-and-build theory of positive emotions,and theoretical framework of ac-ceptability(TFA).Results The international paradigm shifted from focusing on energy consumption to attaching importance of mental health.The population transformed from extensive management to precise intervention.The intervention meth-ods were characteristic of technological integration and system innovation.The assessment system transformed from single-dimension to comprehensive monitoring.The monitoring and evaluation was developing to digitali-zation and collaboration.Chinese policies particularly emphasized the strategic orientations of Strengthening Mind through Physical Activity and Five Ways of Education,stressing daily physical activity and enhancing the mental health service system for college students.SDT highlighted the critical role of intrinsic motivation and the satisfaction of basic psychological needs for sustained participation in physical activity.TPB focused on the pre-dictive effect of attitudes,subjective norms and perceived behavioral control on behavioral intentions and subse-quent behavior.The broaden-and-build theory of positive emotions elucidated how physical activity elicitsed pos-itive emotions,which in turn broaden individuals'thought-action repertoires and build lasting personal resources.TFA analyzed the impact of physical activity from the perspectives of affective attitude,burden,opportunity costs,intervention coherence,self-efficacy,perceived effectiveness and ethicality.Conclusion There is a pivotal role of physical activity in fostering college students'mental and behavioral health.The potential areas for optimization of policies have been identified.SDT,TPB,the broaden-and-build theory of posi-tive emotions,and TFA models can explain and guide physical activity promotion among college students.

Objective To propose a novel method for verifying the isocenter in radiotherapy based on markers and conduct a preliminary test. Methods A feasibility experiment was conducted on wooden box phantom for radiotherapy resetting. Fifteen groups of displacement data were randomly generated,corresponding to the position deviations of the isocenter in the radiotherapy plan relative to the original isocenter. According to each set of displacement data,with the aid of movable lasers and a CT scanning couch,CT scanning was performed with two sets of markers (3 per set) affixed to the phantom which were corresponding to the original and treatment isocenters,respectively. In the Eclipse treatment planning system,the coordinate data of the original and treatment isocenters were manually verified,and the difference of coordinate data was calculated to obtain the actual displacement value. The treatment isocenter position was finally confirmed by comparing with the actual displacement. In addition,the study attempts to use threshold segmentation algorithm to automatically detect metal markers and obtain coordinate values of the original isocenter on patient-positioned CT images. In the wooden box experiment,the absolute value of the difference between the actual displacement value and the planned displacement value (?d) was used to represent the position accuracy of treatment isocenter,and the deviation value obtained with threshold segmentation algorithm for isocenter detection was ?s. Results The ?d in the X (left-right),Y (superior-inferior) and Z (anterior-superior) directions was (0.83±0.37) mm,0 (0,0.5) mm and (0.45±0.29) mm,respectively. The ?s in the X,Y and Z directions was (0.46±0.22) mm,0 (0,0.5) mm and (0.33±0.29) mm,respectively. The mean values of ?s in 3 directions were all lower than 2 mm,within the range of permissible clinical positioning error. Conclusion The method of automatically verifying treatment isocenter position based on markers is feasible,and the study provides a useful reference for radiotherapy resetting using CT simulator.

Objective:To explore the spatial correlation between gray matter volume (GMV) changes and neurotransmitter receptors/transporters in patients with first-episode schizophrenia (FES) .Methods:Fifty-four FES patients(FES group) and fifty-nine healthy controls (HC group) were selected from June 2014 to May 2020 in the Psychiatry Department of Renmin Hospital of Wuhan University. Structural magnetic resonance imaging (sMRI) was conducted on all subjects. Differences of GMV were compared across 400 cortical regions and 32 subcortical regions. Based on the positron emission tomography(PET) data from Neuromaps, which provides the density of 19 different neurotransmitter receptors and transporters, Spearman correlation analysis was performed to evaluate the spatial correlation between GMV changes and neurotransmitter systems.Results:Compared to the HC group, FES group exhibited significant GMV reductions in widespread cortical (90/400) and subcortical (6/32) regions (all FDR-corrected P<0.05). The effect size of GMV reduction (Cohen’s d) showed significant positive correlations with the density of 5-hydroxytryptamine 1a(5HT1a) ( r=0.400, Pspin=0.002), γ-aminobutyric acid type A receptor(GABA A)( r=0.307, Pspin=0.002), and metabotropic glutamate receptor 5(mGluR5) ( r=0.275, Pspin=0.020) receptors (all FDR-corrected P<0.05). Conclusion:GMV reductions in a wide range of brain regions existed in patients with FES. There are significant correlations between 5HT1a, GABA A and mGluR5 receptors and gray matter reduction in patients with FES. The disorder of these neurotransmitter receptors may be the potential neurobiological mechanism of gray matter structural abnormalities in the early stage of schizophrenia.