ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion （MCAO） mice by regulating the expression of neutrophil-related chemokines in exosomes， thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free （SPF） C57BL/6J mice were randomly divided into four groups： Sham-operated group， MCAO model group， Huanglian Jiedutang group （6 g·kg^-1）， and Ginaton group （21.6 mg·kg^-1）， with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·（10 g）^-1 for 7 consecutive days， while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days， MCAO surgery was performed. The distal and proximal ends of the right common carotid artery （CCA） were ligated， a small incision was made between the two ligatures， and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling， mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy， particle size analysis， and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase （MPO） in the brains of mice in each group. ResultsCompared with the sham-operated group， the model group showed decreased neurological function scores （P<0.01）， obvious cerebral infarction （P<0.01）， reduced cerebral blood flow （P<0.01）， neuronal necrosis in the brain， and decreased numbers of Nissl bodies （P<0.01）. The mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were significantly increased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were increased （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were elevated （P<0.01）. Compared with the model group， the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores （P<0.05）， reduced cerebral infarct volume （P<0.01）， restored cerebral blood flow （P<0.01）， reduced necrotic cells in the brain， and increased numbers of Nissl bodies （P<0.01）. In the Huanglian Jiedutang group， the mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were decreased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were reduced （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were decreased （P<0.01）. ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice， thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.

ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion （MCAO） mice by regulating the expression of neutrophil-related chemokines in exosomes， thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free （SPF） C57BL/6J mice were randomly divided into four groups： Sham-operated group， MCAO model group， Huanglian Jiedutang group （6 g·kg^-1）， and Ginaton group （21.6 mg·kg^-1）， with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·（10 g）^-1 for 7 consecutive days， while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days， MCAO surgery was performed. The distal and proximal ends of the right common carotid artery （CCA） were ligated， a small incision was made between the two ligatures， and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling， mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin （HE） staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy， particle size analysis， and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay （ELISA） was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase （MPO） in the brains of mice in each group. ResultsCompared with the sham-operated group， the model group showed decreased neurological function scores （P<0.01）， obvious cerebral infarction （P<0.01）， reduced cerebral blood flow （P<0.01）， neuronal necrosis in the brain， and decreased numbers of Nissl bodies （P<0.01）. The mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were significantly increased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were increased （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were elevated （P<0.01）. Compared with the model group， the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores （P<0.05）， reduced cerebral infarct volume （P<0.01）， restored cerebral blood flow （P<0.01）， reduced necrotic cells in the brain， and increased numbers of Nissl bodies （P<0.01）. In the Huanglian Jiedutang group， the mRNA expression levels of IL-1β， MPO， CXCL1， CXCL2， CXCL3， CXCL10， CCL2， and CCL3 in exosomes from plasma and brain tissues were decreased （P<0.05， P<0.01）. The protein expression levels of IL-1β， MPO， CXCL2， and CXCL10 in exosomes from brain tissues were reduced （P<0.05， P<0.01）， and MPO-positive rates and mean optical density values in brain tissues were decreased （P<0.01）. ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice， thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.

ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

Objectives:This study aims to investigate optimal surgical management strategies for pediatric patients diagnosed with volume-overloaded mitral regurgitation. Methods:A comprehensive retrospective analysis was conducted on a cohort of 110 pediatric patients who underwent primary mitral valve repair for volume-overloaded mitral regurgitation at Fuwai Hospital between April 2020 and March 2022.The cohort,with an average age of(14.5±15.1)months and 38.2%males,was divided into standardized group for patients receiving 3-step standardized mitral valvuloplasty(n=69)and annuloplasty group for patients undergoing annuloplasty only(n=41).After propensity score matching,a total of 38 pairs of patients were included,comparing the primary endpoint(functional mitral failure and postoperative heart failure)between the two groups. Results:Over a median follow-up of 26.3(19.8,32.9)months,and with a median echocardiographic follow-up of 11.9(7.5,14.8)months,no death was recorded.Among the cases,one patient(0.8%)necessitated unplanned reoperation;and seven patients(6.4%)experienced a recurrence of moderate-severe mitral regurgitation as observed through echocardiography beyond 6 months post-surgery.Additionally,nine patients developed heart failure at one month post-discharge.Above events were similar between the two groups.Following propensity score matching,patients in the standardized group demonstrated significantly longer cardiopulmonary bypass and aortic cross-clamp times compared to the annuloplasty group(both P＜0.05),other outcomes were similar between the two groups.Subgroup analysis based on age indicated that infants(＜1 year old)in the standardized group exhibited a significantly lower incidence of major endpoint events compared to the annuloplasty group.Additionally,postoperative echocardiography in annuloplasty group indicated that Z score of left ventricular end diastolic diameter was still greater than 2 during the latest follow-up. Conclusions:Patients with volume-overloaded mitral regurgitation in the standardized group exhibited comparable perioperative recovery and postoperative outcomes as in the annuloplasty group.For pediatric patients suffering from volume-overloaded mitral regurgitation,particularly those under one year of age,the standardized surgical approach exhibited reduced rates of heart failure and major endpoint events,and this strategy is more suitable for this patient group.

Two pediatric heart failure patients were treated with pulmonary artery banding(PAB)at Fuwai Hospital,from December 2021 to January 2022.In the first case,an 8-month-old patient presented with left ventricular non-compaction cardiomyopathy(LVNC),left ventricular systolic dysfunction,ventricular septal defect,and atrial septal defect.The second case was a 4-month-old patient with LVNC,left ventricular systolic dysfunction,and coarctation of the aorta.After PAB,the left ventricular function and shape of both patients were significantly improved,without serious surgery-related complications.In these individual cases of pediatric heart failure,pulmonary artery banding exhibited a more satisfactory efficacy and safety compared to pharmacological treatment,especially for those with unsatisfactory medication results.Future clinical data are needed to promote the rational and broader application of this therapeutic option for indicated patients.

Objective:To explore the anatomic repair strategy for congenital corrected transposition of great arteries (ccTGA).Methods:At the retrospective study, from August 2004 to May 2019, all 120 consecutive ccTGA were included and all accepted anatomic repair. There were 36 cases with with left ventricular outlet obstruction(LVOTO) and cardiac malpositon [ages(4.6±2.2) years, weight(17.7±5.9)kg] underwent the one and a half ventricle repair(hemi-Mustard and bidirectional Glenn procedures combined with the Rastelli), 49 cases[ages(3.4±2.7) years, weight(17.7±11.4)kg] underwent double switch operation(Great artery swtich with Senning operation), 24 cases [ages(5.7±4.3) years, weight(19.1±8.6)kg] with LVOTO and ventricular sept defect(VSD) accepted the Rastelli with Senning operation, and 14 cases with LVOTO and remote VSD [ages(6.9±4.8) years, weight(23.0±12.9)kg] accepted the Double root transposition(DRT) with Senning operation. Follow up data were collected by telephone interviews and echo. The median follow-up time were 49 months varied from 20 to 84 months, 46 months varied from 18 to 108 months, 35 months varied from 7 to 84 months and 98 months varied from 72 to 145 months. Statistical analysis was performed with SPSS 19.0.Results:There were 6 in-hospital deaths and 2 follow-up deaths. The survival probability were(84.0±6.0)% and(84.0±6.0)% at 5 and 10 years after operation. The probability of freedom from re-intervention were(95.0±11.8)% and(89.0±11.8)% at 5 and 10 years after operation. All 6 patients need implant pacemaker for Ⅲ A-V block. Seven patients had moderate or more than moderate tricuspid regurgitation. The left ventricular(systemic ventricle) EF were 0.61±0.09, 0.63±0.08, 0.59±0.01 and 0.65±0.07 in one and a half ventricle repair group, double switch(AS group), Rastelli with Senning(RS group) and DRT with Senning(DS group) patients. There were 1 heart failure in one and a half ventricle repair group, 1 in AS group and 1 in RS group. For 36 pure ccTGA patients, compared with direct double switch patients these patients accepting double switch after pulmonary banding(PAB) had more EF(0.54±0.09 vs. 0.65±0.08, P=0.00). There were significantly less patients need re-operation in one and a half ventricle repair group compared with RS group(0 vs. 13.6%, P=0.03). Conclusion:For ccTGA/LVOTO/cardiac malpositon, the one and a half ventricle repair was ideal strategy with significant less RV-PA conduit stenosis and re-operation. For pure ccTGA patients, second staged double switch after PAB had better long-term heart function. For ccTGA/ LVOTO/ remote VSD patients DRT with Senning was ideal strategy.

Objective    To summarize the reoperation experience for complete atrioventricular septal defect (CAVSD) with severe left atrioventricular valve regurgitation (LAVVR) by standardized mitral repair-oriented strategy. Methods    From 2016 to 2019, 11 CAVSD patients underwent reoperation for severe LAVVR by standardized mitral repair-oriented strategy at Fuwai Hospital, including 5 males and 6 females with a median age of 56 (22-152) months. The pathological characteristics of severe LAVVR, key points of repair technique and mid-term follow-up results were analyzed. Results    The interval time between the initial surgery and this surgery was 48 (8-149) months. The aortic cross-clamp time was 54.6±21.5 min and the cardiopulmonary bypass time was 107.4±38.1 min, ventilator assistance time was 16.4±16.3 h. All patients recovered smoothly with no early or late death. The patients were followed up for 29.0±12.8 months, and the echocardiograph showed trivial to little mitral regurgitation in 5 patients, little regurgitation in 5 patients and moderate regurgitation in 1 patient. The classification (NYHA) of cardiac function was class Ⅰ in all patients. Conclusion    Standardized mitral repair-oriented strategy is safe and effective in the treatment of severe LAVVR after CAVSD surgery, and the mid-term results are satisfied.

Objective    To explore the operative strategy after palliative shunt for correcting congenitally corrected transposition of great artery (cTGA) patients with left ventricular outflow tract obstruction (LVOTO) and cardiac malpostion. Methods    We retrospectively analyzed the clinical data of 54 patients with onsecutive cTGA with LVOTO and cardiac malpositon from June 2011 to May 2019. The patients were devided into two groups. There were 24 patients (16 males and 8 females at mean age of 5.4±2.2 years) who underwent one and a half ventricle repair as a one and half ventricle group. And there were 30 patients (19 males and 11 females at age of 8.6±6.2 years) who underwent one ventricle repair operation as a one ventricle group. Follow-up data were collected by telephone interviews. Results    There was no statistical difference in systemic atrioventricular valve regurgitation and systemic ventricular ejection fraction between the two groups (P>0.05). Compared with one and a half ventricle group, the cardiopulmonary bypass time (CPB) time, mechanical ventilation time and intensive care unit stay were significant shorter than those in the one ventricle group (P<0.05), but prolonged pleural effusions developed more frequently in the one ventricle repair group (P<0.05). There was no in-hospital death but 1 follow-up death in each group. The follow-up time was 49 (17-38) months in the one and half ventricle group at follow-up rate of 93.9%, and 47 (12-85) months at follow-up rate at 90.9% in the one ventricle group. One and a half ventricle group had better systemic ventricular ejection fraction (EF) than that in the one ventricle repair group. And the rate of heart function (NYHA) class Ⅲ and class Ⅳ in one and a half ventricle group was lower than that in the ventricle group. No significant difference of survival and freedom from re-intervention probability between the two groups was found. Conclusion    For patients of correction of cTGA with LVOTO and cardiac malposition after palliative shunt, the one-and-a-half ventricular repair procedure is ideal operative strategy.

Objective    To summarize the clinical outcomes and experience of surgical treatment for patients with complete atrioventricular septal defect (CAVSD) above the optimal age for surgery. Methods    We retrospectively reviewed clinical data of 163 simple type CAVSD patients less than 7 years who underwent operations in Fuwai Hospital from 2002 to 2013. The patients were divided into a normal group (n=84, including 37 males and 16 females with an average age of 7.6±2.7 months) and an over-age group (n=79, including 30 males and 49 females with an average age of 34.6±19.6 months) according to whether the age was more than 1 year. Results    The average aortic cross clamp time (88.3±24.4 min vs. 106.1±35.4 min, P<0.001) and cardiopulmonary bypass time (123.6±31.1 min vs. 142.6±47.1 min, P=0.003) were statistically different between the two groups. During the follow-up period (the normal group 53.3±43.9 months, the over-age group 57.2±48.2 months), there was no statistical difference in all-cause mortality (10.7% vs. 8.9%, P=0.691), the incidence of moderate or severe left atrioventricular valve regurgitation (16.7% vs. 21.5%, P=0.430) and reintervention rate (3.6% vs. 0.0%, P=0.266) between the two groups. No left ventricular outflow tract obstruction and complete atrioventricular block occurred in both groups. Conclusion    For CAVSD children above the optimal age, rational surgical treatments can also achieve satisfying results.

To analyze the mid-long-term outcomes of surgical balloon valvuloplasty (SBV) for right ventricular decompression in the treatment of pulmonary atresia with intact ventricular septum (PA/IVS). Methods    Clinical data of consecutive 91 patients who were diagnosed with PA/IVS and underwent SBV in our institution from January 2005 to December 2017 were retrospectively analyzed, including 52 (57.1%) males and 39 (42.9%) females. The median age was 3 months (1 d, 24 months) and the median weight was 4.1 (2.5, 12.0) kg. Results    The SBV was performed in all patients, and 62 of whom received other simultaneous surgeries, including ligation of patent ductus arteriosus (PDA, 33 patients), ligation of PDA with modified Blalock-Taussig shunt (23 patients), ligation of PDA with bidirectional Glenn shunt (6 patients). There was no early postoperative death. The median follow-up time was 8.8 (2.5, 13.4) years, 4 patients were lost. There were 7 (8.0%) deaths and 1 (1.1%) patient with a re-SBV for pulmonary stenosis. The one and a half ventricular repair was performed in 5 (5.7%) patients and Fontan procedure in 2 (2.3%) patients. In addition, the mean Z-value of tricuspid valve annulus was −1.7±1.5, which was significant bigger than that before the operation (t=5.587, P<0.001). Conclusion    SBV via right ventricular outflow tract for right ventricular decompression in the treatment of PA/IVS is safe and reliable. The majority of patients can receive biventricular repair instead of single ventricular palliation by SBV with individually customized shunt.