ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

OBJECTIVE To investigate the effects of alirocumab combined with atorvastatin on clinical efficacy and safety of patients with acute coronary syndrome （ACS） who underwent percutaneous coronary intervention （PCI）. METHODS A total of 207 patients with ACS who underwent PCI in our hospital from January 2021 to December 2023 were randomly divided into alirocumab group， ezetimibe group and control group， with 69 cases in each group. All patients received routine thrombosis prevention and antihypertensive treatment after PCI. On this basis， patients in the control group were treated with atorvastatin （20 mg/time， once a day）； patients in the ezetimibe group were treated with ezetimibe （10 mg/time， once a day） + atorvastatin （20 mg/time， once a day）； patients in the alirocumab group were treated with alirocumab （75 mg/time， once every 2 weeks） + atorvastatin （20 mg/time， once a day）. All patients in the three groups were treated for 8 weeks and followed up for another 6 months after treatment. The levels of cardiac function and lipid metabolism indices before and after treatment， as well as the occurrence of major adverse cardiovascular event （MACE） and other adverse drug reaction （ADR） during the follow-up period were compared among the three groups. RESULTS After treatment for 8 weeks， the levels of cardiac function and lipid metabolism indices in the three groups were significantly improved compared with those before treatment （P＜0.05）. Compared with the control group and ezetimibe group， the left ventricular ejection fraction in the alirocumab group was significantly increased， and the left ventricular end-diastolic diameter （LVEDD） was significantly shortened （P＜0.05）. Compared with control group， LVEDD of ezetimibe group was significantly shortened （P＜0.05）， the levels of total cholesterol， triglyceride and low-density lipoprotein cholesterol in the alirocumab group and ezetimibe group were significantly decreased （P＜0.05）. During the follow-up period， there was no significant difference in the total incidence of MACE and the total incidence of other ADR such as headache and abdominal pain among the three groups （P＞0.05）. CONCLUSIONS Alirocumab combined with atorvastatin can significantly improve cardiac function and regulate lipid metabolism indices in patients with ACS after PCI without increasing the risk of MACE or other ADR.

Objective:To investigate the clinical characteristics of patients with myocardial infarction with non-obstructive coronary arteries(MINOCA)and the risk factors of major adverse cardiovascular events(MACE)within 1 year of follow-up.Methods:A total of 1 866 patients who met the diagnosis of acute myocardial infarction and underwent coronary angiography in the Department of Cardiovascular Medicine of our hospital from Sep 2018 to Sep 2021 were selected.According to the results of coronary angiography,the patients were divided into MINOCA group and myocardial infarction with obstructive coronary artery disease(MI-CAD)group.The clinical characteristics and the occurrence of MACE in the two groups were compared.According to the occurrence of MACE,patients in MINOCA group were divided into MACE group and non-MACE group.Binary logistic regression analysis was used to explore the risk factors for MACE in MINOCA patients.Results:The age of patients in MINOCA group was lower than that in MI-CAD group,and more patients were female(P＜0.05).The risk factors of cardiovascular diseases in MINOCA group were less than those in MI-CAD group(P＜0.05).Some indexes of laboratory were lower than those in MI-CAD group(P＜0.05).Left ventricular ejection fraction(LVEF)were higher than that in MI-CAD group(P＜0.05).Left ventricular end-diastolic inner diameter(LVEDD)was lower than that in MI-CAD group,and the proportion of patients with abnormal ventricular wall motion and high cardiac function grade was lower than that in MI-CAD group,and the difference was statistically significant(P＜0.05).The 1-year follow-up showed no significant difference in the incidence of MACE between the two groups(P=0.115).Binary logistic regression analysis showed that smoking(OR=13.095,95%CI:1.799-7.398)and low LVEF(OR=0.036,95%CI:0.012-0.679)were independent risk factors for MACE in MIONCA patients.Conclusions:MINOCA patients are more common in women,with lower age and fewer cardiovascular risk factors,but the incidence of MACE is not less than that of MI-CAD patients.Smoking and low LVEF are independent risk factors for MACE in MINOCA patients.

OBJECTIVE To study the effects of Zigui yichong formula on premature ovarian insufficiency （POI） in mice through glycolysis metabolic pathway. METHODS Eighty SPF C57BL/6N female mice were divided into normal group， model group， Zigui yichong formula group （14.175 g/kg）， Zigui yichong formula+2-deoxy-D-arabino-hexose （2-DG） group （Zigui yichong formula 14.175 g/kg + glycolysis inhibitor 2-DG 100 mg/kg）， with 20 mice in each group. Except for the normal group， POI model mice were induced by intraperitoneal administration of cyclophosphamide in the other groups. After the model was successfully established， each group was given corresponding drugs. HE staining was employed to observe the pathomorphological changes in ovarian tissue and to count follicles at all developmental stages； radioimmunoassay was conducted to measure the serum levels of estradiol （E2）， anti-Müllerian hormone （AMH）， and follicle-stimulating hormone （FSH）； TUNEL assay was employed to detect apoptosis in ovarian granulosa cells of mice； the activities of hexokinase （HK）， pyruvate kinase （PK） and lactate dehydrogenase （LDH） were detected by colorimetry； Western blot and real-time fluorescence quantitative PCR were employed to analyze the protein and mRNA expressions of B-cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， caspase-3， HK2， pyruvate kinase M2 （PKM2）， and lactate dehydrogenase A （LDHA）. RESULTS Compared with model group， the number of primordial follicles， growing follicles， antral follicles and granulosa cells were increased significantly（P＜0.05）， and granulosa cells arranged neatly， but the number of atretic follicles and granulosa cells apoptosis were decreased significantly in Zigui yichong formula group （P＜0.05）； the serum levels of E2 and AMH， the activities of HK， PK and LDH， protein and mRNA expressions of Bcl-2， HK2， PKM2 and LDHA were increased significantly （P＜0.05）； the serum levels of FSH， the protein and mRNA expressions of Bax and caspase-3， Bax/Bcl-2 ratio were decreased significantly （P＜0.05）. 2-DG could reverse the improvement effects of Zigui yichong formula on the above indexes of POI model mice. CONCLUSIONS Zigui yichong formula may inhibit the apoptosis of ovarian granulosa cells， reduce follicle atresia and improve ovarian reserve function by promoting glycolysis levels in POI model mice.

This paper summarizes the exploration process and academic significance of the academic thought of Zhou Zhongying,a master of traditional Chinese medicine,who took the creation of a new system of TCM pathogenesis theory as the core,and interprets its theoretical connotation.As a pioneer in the construction of higher education textbooks for traditional Chinese medicine,Professor Zhou Zhongying created the outline of TCM internal medicine viscera differentiation,persisted in carrying out innovative research on patho-genesis theory,achieved fruitful academic results,and enriched and developed the academic system of TCM theory.In the clinical di-agnosis and treatment of exogenous febrile diseases and acute and difficult internal injuries,he systematically created new pathogenesis theories such as stasis-heat theory and cancer toxicity theory.Based on this,the legislation of medication can improve the clinical effi-cacy,and it is realized that identifying the pathogenesis is the key link in syndrome differentiation and treatment.In his later years,Professor Zhou Zhongying,guided by the holistic view,proposed the"thirteen pathogenesis"and constructed a new system of TCM pathogenesis differentiation,highlighting the guiding value of complex pathogenesis and the causal chain of pathogenesis elements to complex clinical diseases and syndromes,forming a theory with the idea of"examining syndromes and seeking pathogenesis,activating syndrome differentiation"as its soul.This theory breaks through the rigid thinking of syndrome differentiation and treatment based on a single pathogenesis or fixed syndrome type,reconstructs the theoretical framework of TCM with the idea of holistic view,and is a major academic innovation in modern TCM.

Objective To construct a predictive model for the risk of non-suicidal self-injury(NSSI)in young and middle-aged patients with major depressive disorder based on the decision tree algorithm.Methods Young and middle-aged patients with major depressive disorder admitted to the Chongqing Mental Health Center from January 2021 to June 2023 were selected as the research subjects and their clinical data were collected.According to whether NSSI occurred or not,the patients were divided into the NSSI group(n=72)and the non-NSSI group(n=82).Univariate and multivariate logistic regression analyses were used to analyze the risk factors of NSSI in young and middle-aged patients with major depressive disorder.A deci-sion tree predictive model was established based on the results of logistic regression analysis and the Chi-square Automatic Interaction Detection(CHAID)algorithm.The predictive value of the model was evaluated using Receiver Operating Characteristic(ROC)curve.Results The incidence of NSSI in 154 young and mid-dle-aged patients with major depressive disorder was 46.8％.The results of single-factor analysis showed that there were no statistically significant differences(P＞0.05)in gender,age,education level,occupation,family composition,only child status,relationship status,fertility status,main place of residence,family economic source,and housing conditions between the two groups.Statistically significant differences(P＜0.05)were observed in living conditions,family economic status,duration of depression,SSRS score,PSS-Fa score,and DS score between the two groups.Multi-factor logistic regression analysis showed that lower family economic lev-el,longer duration of depression,SSRS score＜20 points,PSS-Fa score＜6 points,and DS score ≥47.2 points were independent risk factors for NSSI in young and middle-aged patients with major depressive disorder(P＜0.05).The constructed decision tree model had five layers and ten nodes,with family economic situation,duration of depression,SSRS score,and PSS-Fa score selected as the nodes of the model,among which the PSS-Fa score was the most important predictive factor.ROC curve analysis showed that the AUC of the model was 0.881(95％CI:0.844-0.918).Conclusion There are many influencing factors for the occurrence of NSSI in young and middle-aged patients with major depressive disorder.The decision tree model constructed based on these factors has a high predictive value for the risk of NSSI in young and middle-aged patients with major depressive disorder.

Objective:To conduct systematic review of mother-infant attachment measurement tools based on Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) guidelines.Methods:The researches on mother-infant attachment measurement tools in PubMed, Scopus, Embase, Web of Science, China Biology Medicine disc, China National Knowledge Infrastructure, WanFang Data and VIP was searched by computer, and the search period was from establishment of the databases to October 30, 2023. Two reviewers trained in evidence-based methodology independently screened the literature, extracted and summarized the data, and systematically evaluated the attributes of the measurement tools using the COSMIN guideline bias risk list and good measurement attribute standards.Results:A total of 35 studies were included, including seven maternal-infant attachment measurement tools. Among them, the content validity quality of the Maternal-fetal Attachment Tool was sufficient (evidence quality was advanced), the structural validity quality was uncertain (evidence quality was intermediate), the internal consistency quality was sufficient (evidence quality was advanced) and the hypothesis testing quality was sufficient (evidence quality was advanced), which was recommended at level A.Conclusions:This study systematically evaluates seven measurement tools for maternal-infant attachment, among which the Maternal-fetal Attachment Tool is class A tool and is recommended for use.

OBJECTIVE To study the protective effects of mangiferin against oxidative stress injury of myocardial cells induced by hydrogen peroxide （H2O2）， and its effects on the expression of nuclear factor of activated T cell cytoplasmic 4（NFATc4）. METHODS H9c2 myocardial cells were cultured in vitro and divided into blank group， H2O2 group， and 50， 100， 150 μmol/L mangiferin groups. Mangiferin groups were treated with different concentrations of mangiferin for 12 h， and then were subjected to H2O2 （200 μmol/L） stimulation for 12 hours together with the H2O2 group； relative survival rate was detected in each group， and the levels of superoxide dismutase （SOD）， catalase （CAT） and malondialdehyde （MDA） in cell supernatant and reactive oxygen species （ROS） in H9c2 cells were measured. Meanwhile， the expressions of apoptosis-related proteins [B cell lymphoma 2 （Bcl- 2）， Bcl-2 associated X protein （Bax）， cleaved caspase-3] and nuclear protein NFATc4 were determined. Furthermore， the NFATc4 interference sequence was transfected， and the effects of NFATc4 on oxidant stress indexes and apoptosis-related proteins in H2O2- induced myocardial cells were investigated. RESULTS Compared with blank group， relative cell viability， the levels of SOD and CAT， relative expression of Bcl-2 were decreased significantly， while the levels of MDA and ROS， relative expressions of Bax， cleaved caspase-3 and nuclear protein NFATc4 were increased significantly （P＜0.05 or P＜0.01）. Compared with the H2O2 group， the above indexes of 100 and 150 μmol/L mangiferin groups were reversed significantly （P＜0.05）. After the transfection of the NFATc4 interference sequence， the expression of nuclear protein NFATc4 was down-regulated significantly； the levels of MDA and SOD， the protein expressions of Bax and cleaved caspase-3 were all decreased/down-regulated significantly， while the levels of SOD and CAT， and the protein expression of Bcl-2 were all increased/up-regulated significantly， compared with H2O2 group （P＜ 0.05）. CONCLUSIONS Mangiferin can relieve H2O2-induced oxidative stress of H9c2 cells， reduce the apoptosis and inhibit the nuclear translocation of NFATc4， thereby alleviating myocardial cell damage； reducing the nuclear level of NFATc4 protein is related to reducing H2O2-induced oxidative stress and cell apoptosis.

BackgroundHome-based intervention occupies a prominent place in the treatment of autism spectrum disorder （ASD） in children， whereas previous studies on the effect of home-based early intensive behavioral intervention on verbal ability of children with ASD are somewhat inadequate. ObjectiveTo study the effects of intensive family behavioral of intervention based on Verbal Behavior Milestones Assessment and Placement Program （VB-MAPP） on the language ability of children with ASD， so as to provide references for the development of family intervention strategies for children with ASD. MethodsChildren aged 2 to 3 years old who attended the Children's Rehabilitation Department of the Second Affiliated Hospital of Shantou University Medical College from September 2020 to December 2021 and met the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） diagnostic criteria for ASD were selected as the study objects. A non-randomized concurrent control trial was conducted to compare a study group （n=24） receiving home-based early intensive behavioral intervention using VB-MAPP with a control group （n=14） receiving training from other special institutions or early childhood education institutions. The intervention lasted for 6 months in both groups. Before and after the intervention， the VB-MAPP milestone assessment was performed in the two groups， and the VB-MAPP milestone score， mand， trac and listener responds were selected as the study indicators. Then the intervention effect was compared between two groups， and the multiple linear regression was performed to screen the related influencing factors. ResultsAfter intervention， the total milestone assessment score， mand， tact and listener responds scores of study group were higher than those of control group， with statistical difference （Z=-4.339~-2.195， P<0.05 or 0.01）. Multiple linear regression analysis denoted that the average weekly hours of home-based intervention in the first three months had certain effect on listener responds （β=1.029， P<0.05）. ConclusionApplication of home-based early intensive behavior intervention using VB-MAPP may contribute to the improvement of verbal abilities such as mand， tact and listener responds in children with ASD. ［Funded by 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund （number， 20200601）］

OX40 is a costimulatory receptor that is expressed primarily on activated CD4⁺, CD8⁺, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.
Mice ; Animals ; Receptors, Tumor Necrosis Factor/physiology* ; Receptors, OX40 ; Membrane Glycoproteins ; Ligands ; Antibodies, Monoclonal/pharmacology* ; Antineoplastic Agents/pharmacology*