Objective To observe the effects of Levo-tetrahydropalmatine(l-THP)on the expression,regression and relapse of conditioned place preference(CPP)in ketamine induced rats,and to detect the content of dopamine(DA)in the striatum(caudate putamen,CPu)of the rat brain at different time points.Methods Ketamine addiction rat model was established by CPP.The effects of l-THP on the expression,regression and relapse of ketamine induced rat CPP were investigated using CPP score as the index.The content of DA in CPu of rats was determined by ultra-performance liquid chromatography coupled to tandem mass spectrometry(UPLC-MS/MS)after ketamine administration and l-THP intervention at 30 min,60 min,90 min,120 min and 150 min.Results It indicated that 1-THP could decrease the expression of CPP in ketamine induced rats,promote the process of CPP resolution and inhibit the process of relapse.In addition,l-THP combined with ketamine administration significantly inhibited the ketamine-induced increase in DA content in the CPu of the rats.Conclusion The mechanism of l-THP inhibiting the reward effect of ketamine may be related to blocking DA receptors and reducing the release of DA neurotransmitters.l-THP has potential implications for the treatment of ketamine addiction.

The consensus was authored by National Society of Congenital Heart Diseases. After employing the Delphi process and incorporating literature reviews and expert discussions, seven recommendations were ultimately formulated. The consensus provides a detailed elaboration on the pathoanatomy, pathophysiology, clinical manifestations, diagnostic methods, and surgical treatment approaches for aortic valve diseases in children. It emphasizes that the treatment of aortic valve diseases in children should take into account the needs of growth and development, and recommends surgical strategies for different age groups and types of lesions, including valve plasty, Ross procedure, valve replacement, and balloon dilation. Specifically, aortic valve plasty is recommended for neonates and infants, while surgical options for older children are more diversified. The consensus only discusses isolated aortic valve disease and does not cover cases complicated with other heart malformations

Endoplasmic reticulum(ER)is the predominant membrane structure in eukaryotic cells and is a key or-ganelle for the occurrence of important intracellular physiological processes.Under the action of various internal and ex-ternal factors,the homeostasis of ER is disrupted to block protein processing and transport,and the accumulation of unfol-ded or misfolded proteins in the ER lumen,forms endoplasmic reticulum stress(ERS)and triggers the unfolded protein re-sponse(UPR).Moderate ERS reduces protein synthesis,promotes protein degradation,and increases molecular chaper-ones that assist protein folding through the UPR signaling pathway,ultimately relieving ER stress.However,if the ERS is too strong or prolonged and exceeds the cell's ability to regulate itself,the UPR can initiate apoptosis and lead to diseases.Numerous studies have shown that ERS is closely associated with the development of several cardiovascular diseases(CVD).This review focuses on the research progress of UPR in several common types of CVD and targets UPR as a po-tential therapeutic approach for CVD.

Objective:To explore the difference of inflammatory factor imbalance between adolescent and adult patients with depression.Methods:A total of 30 adolescent and 30 adult patients with depression, and 30 adolescent and 30 adult healthy controls were included from January 2022 to August 2023. Interleukin-6 (IL-6), interleukin-17 (IL-17), transforming growth factor-beta1(TGF-β1), interleukin-10(IL-10) and Maresin-1(MaR1) level were detected by enzyme-linked immunosorbent assay. 24-item Hamilton depression scale (HAMD-24) was used to assess the severity of depression in all depressed patients. SPSS 26.0 statistical software was used for t-test, covariance analysis, Spearman analysis and multivariate binary logistic regression, and the predictive value of selected inflammatory factors in depression was evaluated by receiver operating characteristic(ROC) curve. Results:(1)In adolescent group, the levels of IL-6 ((64.000±38.632) pg/mL), IL-17((239.132±49.757) pg/mL), and TGF-β1((737.267±328.447)pg/mL) in patients with depression were higher than those in control group((32.396±16.330)pg/mL, (214.954±42.326)pg/mL, (454.542±297.194)pg/mL, all P<0.05), while the level of MaR1((21 381.301±3 946.011)pg/mL) was significantly lower than that in control group((30 130.138±10 278.999)pg/mL)( P<0.001). The level of IL-17 was positively correlated with the total score of HAMD-24 ( r=0.429) and the course of disease ( r=0.571), the level of IL-10 was negatively correlated with body weight factor score ( r=-0.384), and the levels of TGF-β1 was negatively correlated with anxiety/somatization factor score ( r=-0.449)(all P<0.05) in adolescent patients with depression.MaR1( B=0.000 1, OR=0.999 8, AUC=0.794, P<0.05) was an independent risk factor for adolescents depression.(2)In adult depression group, the levels of IL-6, IL-17, IL-10, TGF-β1 and MaR1 were higher than those in adult control group(all P<0.05). The level of TGF-β1 in adult depression group was negatively correlated with the total score of HAMD-24 ( r=-0.427), the score of anxiety/somatization factor ( r=-0.368), the score of blocking factor ( r=-0.405), and the score of hopelessness factor ( r=-0.398).The level of MaR1 was positively correlated with the age of onset of disease ( r=0.425)(all P<0.05) in adult patients with depression.MaR1( B=0.000 4, OR=1.000 3, AUC=0.874, P<0.001) and IL-6( B=0.040, OR=1.040 7, AUC=0.779, P<0.05) were independent risk factors for adult depression.The AUC of IL-6 combined with MaR1 was 0.938. Conclusion:There are differences in the underlying mechanism of immune imbalance between adolescent and adult patients with depression.MaR1 may be a diagnostic biomarker for depression in adolescents and adults.

Objective:To investigate the relationship between serum soluble CD155 (sCD155), soluble CD163 (sCD163) and chemotherapy efficacy and prognosis in patients with diffuse large B-cell lymphoma (DLBCL).Methods:A total of 126 patients with DLBCL admitted to Handan Central Hospital from May 2018 to May 2020 (DLBCL group) and 126 healthy subjects (control group) were prospectively selected to compare serum sCD155 and sCD163 levels. According to the chemotherapy effect of DLBCL patients, they were divided into effective group and ineffective group, and the serum sCD155 and sCD163 levels were compared before and after treatment. The effective rate of chemotherapy in patients with different serum sCD155 and sCD163 levels was compared. Kaplan-Meier method was used to analyze the relationship between serum sCD155 and sCD163 levels and 3-year overall survival (OS) and progression-free survival (PFS) of DLBCL patients. Cox proportional risk regression model was used to analyze the prognostic factors of DLBCL patients.Results:The serum levels of sCD155 and sCD163 in DLBCL group were higher than those in control group before treatment (all P<0.05). The effective rate of chemotherapy in 126 DLBCL patients in this group was 69.8%(88/126). Compared with the effective group, the serum levels of sCD155 and sCD163 were higher in the ineffective group before and after treatment (all P<0.05). Compared with before treatment, serum sCD155 and sCD163 levels in the effective group were decreased after treatment (all P<0.05). The effective rate of DLBCL patients in sCD155 and sCD163 high level groups was lower than that in sCD155 and sCD163 low level groups (all P<0.05). Kaplan-Meier analysis showed that the 3-year OS and PFS of DLBCL patients in the low level group of sCD155 and sCD163 were higher than those in the high level group (all P<0.05). The high level of sCD155 and sCD163 were independent risk factors for 3-year PFS and OS in DLBCL patients (all P<0.05). Conclusions:Abnormal levels of serum sCD155 and sCD163 in DLBCL patients may reduce the efficacy of chemotherapy and lead to poor prognosis.

Objective    To compare the long-term durability of valved homograft conduit (VHC) in patients with Ross and non-Ross right ventricular outflow tract (RVOT) reconstruction. Methods    Patients who underwent RVOT reconstruction using VHC in Fuwai Hospital from January 2008 to October 2020 were retrospectively included. Patients who received Ross RVOT reconstruction were allocated to a Ross group and patients who received non-Ross RVOT reconstruction were allocated to a non-Ross group. The survival and reintervention-free rates of the two groups were evaluated with the Kaplan-Meier survival curve and log-rank test. The propensity score matching analysis was performed on the patients who completed ultrasound follow-up in the two groups, and the VHC dysfunction-free rate was compared between the two groups. Results    A total of 243 patients were enrolled, including 142 males and 101 females, with a median age of 6 years (4 months to 56 years). There were 77 patients in the ROSS group and 166 patients (168 operations) in the non-ROSS group. The cardiopulmonary bypass time in the Ross group was shorter than that in the non-Ross group (175.4±45.6 min vs. 200.1±83.5 min, P=0.003). Five patients in the non-Ross group died early after the operation. The follow-up was available in 231 patients (93.1%), with the average follow-up time of 61.7±44.4 months. During the follow-up, 5 patients in the non-Ross group died. The 12-year survival rate was 100.0% in the Ross group and 93.2% in the non-Ross group (log-rank, P=0.026). In addition, 1 patient in the Ross group and 7 patients in the non-Ross group received VHC reintervention. There was no significant difference in the reintervention-free rate between the two groups (log-rank, P=0.096). Among the 73 patients in the Ross group and 147 patients in non-Ross group who were followed up by ultrasound after discharge, 45 patients (20.5%) developed VHC dysfunction. Before matching, the long-term durability of VHC in the Ross group was better than that in non-Ross group (10-year VHC dysfunction-free rate: 66.6% vs. 37.1%, log-rank, P=0.025). After the propensity score matching, 64 patients included in each group, and there was no statistical difference in the long-term durability of VHC between the two groups (10-year VHC dysfunction-free rate: 76.3% vs. 43.0%, log-rank, P=0.065). In the subgroup analysis, the 10-year VHC dysfunction-free rate in the Ross group was higher than that in the non-Ross group (71.0% vs. 20.0%, log-rank, P=0.032) among patients aged<6 years at surgery. However, there was no significant difference in the 10-year VHC dysfunction-free rate between the two groups (53.7% vs. 56.7%, log-rank, P=0.218) among patients aged ≥6 years at surgery. Conclusion    After the propensity score matching analysis, the long-term durability of VHC has no significant difference between the Ross group and non-Ross group. The long-term durability of VHC after Ross surgery is superior to that of non-Ross surgery in patients aged<6 years at surgery.

Objective    To evaluate the clinical outcome of valved homograft conduits (VHC) used for right ventricular outflow tract (RVOT) reconstruction in Fuwai Hospital in recent 13 years, and explore the factors influencing the long-term durability of VHC. Methods    Clinical data of patients using VHC for RVOT reconstruction in Fuwai Hospital from November 2007 to October 2020 were retrospectively analyzed. The Kaplan-Meier survival curve was used to evaluate survival, VHC reintervention and VHC dysfunction. Cox proportional risk regression model was used to analyze the risk factors for VHC dysfunction. Results    Finally 251 patients were enrolled, including 145 males and 106 females. The median age at surgery was 6.0 (0.3-67.0) years. Early death occurred in 5 (2.0%) patients. The follow-up was available for 239 (95.2%) patients, with the follow-up time of 0.3-160.0 (61.3±45.4) months. Five patients died during the follow-up, and the 1-year, 6-year, and 13-year survival rates were 96.6%, 95.5% and 95.5%, respectively. Eight patients received VHC reintervention during the follow-up, and freedom rates from VHC reintervention were 100.0%, 97.1% and 82.4% at 1 year, 6 years and 13 years, respectively. A total of 226 patients were followed up by echocardiography after discharge, with the follow-up time of 0.2-138.0 (48.5±40.5) months. During the follow-up, 46 (20.4%) patients developed VHC dysfunction, and freedom rates from VHC dysfunction at 1 year, 5 years, and 10 years were 92.6%, 79.6% and 59.3%, respectively. Univariate Cox regression analysis showed that age<6 years and VHC diameter<19 mm were risk factors for VHC dysfunction (P=0.029, 0.026), but multivariate regression analysis only indicated that age<6 years was an independent risk factor for VHC dysfunction (P=0.034). Conclusion    The early and late outcomes of VHC used for RVOT reconstruction are satisfactory, and the long-term durability of VHC is also optimal. In addition, age<6 years is an independent risk factor for VHC dysfunction.

OBJECTIVE: Diterpenoids with a wide variety of biological activities from Anoectochilus roxburghii, a precious medicinal plant, are important active components. However, due to the lack of genetic information on the metabolic process of diterpenoids in A. roxburghii, the genes involved in the molecular regulation mechanism of diterpenoid metabolism are still unclear. This study revealed the complex metabolic genes for diterpenoids biosynthesis in different organs of A. roxburghii by combining analysis of transcriptomics and metabolomics. METHODS: The differences in diterpenoid accumulation in roots, stems and leaves of A. roxburghii were analyzed by metabonomic analysis, and its metabolic gene information was obtained by transcriptome sequencing. Then, the molecular mechanism of differential diterpenoid accumulation in different organs of A. roxburghii was analyzed from the perspective of gene expression patterns. RESULTS: A total of 296 terpenoid metabolites were identified in the five terpenoid metabolic pathways in A. roxburghii. There were 38, 34, and 18 diterpenoids with different contents between roots and leaves, between leaves and stems, and between roots and stems, respectively. Twenty-nine metabolic enzyme genes with 883 unigenes in the diterpenoid synthesis process were identified, and the DXS and FDPS in the terpenoid backbone biosynthesis stage and CPA, GA20ox, GA3ox, GA2ox, and MAS in the diterpenoid biosynthesis stage were predicted to be the key metabolic enzymes for the accumulation of diterpenoids. In addition, 14 key transcription factor coding genes were predicted to be involved in the regulation of the diterpenoid biosynthesis. The expression of genes such as GA2ox, MAS, CPA, GA20ox and GA3ox might be activated by some of the 14 transcription factors. The transcription factor NTF-Y and PRE6 were predicted to be the most important transcription factors. CONCLUSION This study determined 29 metabolic enzyme genes and predicted 14 transcription factors involved in the molecular regulation mechanism of diterpenoid metabolism in A. roxburghii, which provided a reference for the further study of the molecular regulation mechanism of the accumulation of diterpenoids in different organs of A. roxburghii.

ObjectiveTo investigate the mechanism of Chaihu Shugansan in the treatment of functional dyspepsia in rats based on mitophagy and PTEN-induced kinase 1 （Pink1）/E3 ubiquitin ligase （Parkin）. signaling pathway. MethodAccording to the principle of random grouping， 40 SD rats were assigned into a normal group， a model group， a Chaihu Shugansan group， and a positive drug （domperidone） group， with 10 rats in each group. The rats in other groups except the normal group received tail-clamping stimulation to replicate the model of functional dyspepsia. After each time of stimulation， the rats in the normal， model， Chaihu Shugansan， and positive drug groups were administrated with normal saline， normal saline， Chaihu Shugansan （4.8 g·kg^-1）， and an aqueous solution of domperidone （4.5 mg·kg^-1）， respectively. After 28 days of modeling， the gastric emptying rate and the small intestine propulsion rate of the rats in each group were measured and the tissue samples were collected. Hematoxylin-eosin （HE） staining was employed for observation of damage in gastric antrum tissue， and transmission electron microscopy （TEM） for ultrastructural observation of gastric interstitial cells of Cajal （ICCs）. Immunofluorescence co-localization was adopted to observe the expression of cytochrome c oxidase （COX Ⅳ） and Parkin. Western blot was employed to determine the expression levels of microtubule-associated protein 1， light chain 3 （LC3）， and the mitophagy-associated proteins prohibitin2 （PHB2）， Pink1， Parkin， and ubiquitin-specific protease 30 （USP30）. ResultCompared with the normal group， the modeling decreased the gastric emptying rate and the small intestine propulsion rate （P<0.05）. Compared with the model group， Chaihu Shugansan increased the gastric emptying rate and the small intestine propulsion rate （P<0.05）. The results of TEM showed that Chaihu Shugansan reduced the swelling degree of mitochondria in gastric antrum tissue. Compared with the normal group， the modeling increased the fluorescence intensity of Parkin in mitochondria （P<0.01）， while such increase can be alleviated by Chaihu Shugansan （P<0.01）. Western blotting results showed that compared with the normal group， the modeling up-regulated the protein levels of LC3， Pink1， Parkin， and PHB2 （P<0.05， P<0.01） and down-regulated the protein level of USP30 （P<0.01）. Compared with the model group， Chaihu Shugansan down-regulated the protein levels of LC3， Pink1， Parkin， and PHB2 （P<0.05， P<0.01） and up-regulated the protein level of USP30 （P<0.01）. ConclusionChaihu Shugansan may treat functional dyspepsia by blocking the Pink1/Parkin signaling pathway to inhibit excessive mitochondrial autophagy in ICCs.

Objective:To investigate the prognosis and risk factors for children diagnosed with all types of subaortic stenosis(SAS) who developed recurrent left ventricular outflow tract obstruction after surgical treatment.Methods:The study retrospectively included patients aged 0-18 years old who underwent open heart SAS surgery at Fuwai Hospital from 2016-2019. Children with hypertrophic obstructive cardiomyopathy were excluded. Detailed operative notes, medical records and ultrasound information, and follow-ups were extracted. Recurrent SAS was defined as left ventricular outflow tract gradient 30 mmHg(1 mmHg=0.133 kPa) 1 month after SAS surgical treatment.Results:A total of 137 children were included in this study. The medium age of children at the time of SAS surgery was 4.6 years old(3 months-17.8 years old). After a median follow-up of 4.36 years(3.2-5.7 years), a total of 30 patients developed recurrent LVOTO, with a recurrence rate of 21.9%, and 7(5.1%) underwent a second surgery. Compared to the non-recurrent group, children in the recurrent group were younger at the time of surgery( P=0.0443), had a smaller body surface area( P=0.0485), and a longer length of stay( P=0.0380). In Cox analysis, when only considering preoperative variables, the independent risk factor for LVOTO recurrence were a peak left ventricular outflow tract gradient higher than 50 mmHg( HR=5.25, P=0.001), a BSA less than 0.9( HR=2.5, P=0.023), and a length of SAS 5 mm( HR=2.29, P=0.050). When both preoperative and intraoperative variables were considered, preoperative peak left ventricular outflow tract gradient 50 mmHg( HR=4.91, P=0.002) and peeling from the aortic valve( HR=3.23, P=0.010) were independent risk factors for postoperative recurrence. Conclusion:Recurrent LVOTO after SAS surgical repair is common, and regular postoperative follow-up is crucial to evaluate whether a secondary intervention is required. Regular postoperative follow-up is needed for children at high risk.