Objective To explore growth pattern of neo-aortic root as well as development of neo-aortic regurgitation after arterial switch operation (ASO) for Taussig-Bing anomaly. Methods From 2002 to 2017, the patients who received ASO, and were discharged alive from Shanghai Children’s Medical Center and followed up for more than 3 years were retrospectively involved in this study. Results A total of 127 patients were enrolled. There were 98 (77.2%) males, the median age at ASO was 73.0 d and the average weight was 4.7 kg. Forty-five (35.4%) children were complicated with mild or mild-to-moderate pulmonary insufficiency (PI) before ASO. The average follow-up time was 7.0 years. During the follow-up, 14 (11.0%) children presented moderate or greater neo-aortic regurgitation (neo-AR). The diameter of neo-aortic annulus and sinus of Valsalva was beyond normal range during the entire follow-up. The average diameter of neo-aortic annulus was 18.0 mm at 5 years and 20.5 mm at 10 years. The average diameter of sinus of Valsalva was 25.9 mm at 5 years and 31.1 mm at 10 years. Neo-AR continued to develop over time. The diameter of children who developed moderate or greater neo-AR was constantly larger than that of children who did not (χ2=18.3, P<0.001). Preoperative mild or mild-to-moderate PI was an independent risk factor for the development of moderate or greater neo-AR during mid-to-long term follow-up (c-HR=3.46, P=0.03). Conclusion The diameters of neo-aortic annulus and sinus of Valsalva of Taussig-Bing children who receive ASO repair continue to expand without normalization. The dilation of annulus correlates with the development of neo-AR. PI before ASO repair increases the risk of neo-AR development.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective    To explore the effect of LeCompte maneuver on in-hospital mortality and mid-to-long term reintervention after single-stage arterial switch operation in children with side-by-side Taussig-Bing anomaly. Methods     Clinical data of patients diagnosed with side-by-side Taussig-Bing anomaly and undergoing single-stage arterial switch operation in Shanghai Children’s Medical Center from 2006 to 2017 were retrospectively analyzed. Patients were divided into two groups based on whether LeCompte maneuver was performed: a LeCompte maneuver group and a non LeCompte maneuver group. The clinical data of two groups were compared. Results    Finally 92 patients were collected. LeCompte maneuver was performed in 32 out of 92 patients with a median age of 65.0 days and an average weight of 4.3 kg, among whom 24 (75.0%) were male. Fifteen (46.9%) patients received concomitant aortic arch repair while 12 (37.5%) patients were associated with coronary artery malformation. LeCompte maneuver was not performed in 60 patients with a median age of 81.0 days and an average weight of 4.8 kg, among whom 45 (75.0%) were male. Twenty-two (36.7%) patients received concomitant aortic arch repair while 35 (58.3%) patients were associated with coronary artery malformation. The average cardiopulmonary bypass duration of the LeCompte maneuver group showed no statistical difference from the non LeCompte maneuver group (179.0±60.0 min vs. 203.0±74.0 min, P=0.093). The in-hospital mortality of the two groups were 6 (18.8%) and 7 (11.7%), respectively, which also showed no statistical difference (P=0.364). The median follow-up period was 4.1 (1.6, 7.5) years for 79 patients with 8 lost to follow-up, and no death was observed. Kaplan-Meier curve and log-rank test showed no statistical difference in overall mid-to-long term reintervention rate (P=0.850) as well as right ventricular outflow tract and pulmonary artery reintervention rate (P=0.240) with or without LeCompte maneuver. Conclusion    Whether or not to perform LeCompte maneuver shows no statistical impact on in-hospital mortality and mid-to-long term reintervention rate of single-stage arterial switch operation for side-by-side Taussig-Bing anomaly.

Immunoglobulin (IgG) glycosylation affects the effector functions of IgG in a myriad of biological processes and has been closely associated with numerous autoimmune diseases, including systemic lupus erythematosus (SLE), thus underlining the pathogenic role of glycosylation aberration in autoimmunity. This study aims to explore the relationship between IgG sialylation patterns and lupus pregnancy. Relative to that in serum samples from the control cohort, IgG sialylation level was aberrantly downregulated in serum samples from the SLE cohort at four stages (from preconception to the third trimester of pregnancy) and was significantly associated with lupus activity and fetal loss during lupus pregnancy. The type I interferon signature of pregnant patients with SLE was negatively correlated with the level of IgG sialylation. The lack of sialylation dampened the ability of IgG to suppress the functions of plasmacytoid dendritic cells (pDCs). RNA-seq analysis further revealed that the expression of genes associated with the spleen tyrosine kinase (SYK) signaling pathway significantly differed between IgG- and deSia-IgG-treated pDCs. This finding was confirmed by the attenuation of the ability to phosphorylate SYK and BLNK in deSia-IgG. Finally, the coculture of pDCs isolated from pregnant patients with SLE with IgG/deSia-IgG demonstrated the sialylation-dependent anti-inflammatory function of IgG. Our findings suggested that IgG influences lupus activity through regulating pDCs function via the modulation of the SYK pathway in a sialic acid-dependent manner.
Humans ; Pregnancy ; Female ; Lupus Erythematosus, Systemic/pathology* ; Signal Transduction ; N-Acetylneuraminic Acid/metabolism* ; Immunoglobulin G ; Dendritic Cells/pathology*

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68⁺ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

Objective    To discuss outcomes of arch reintervention for post-repair recoarctation in children. Methods    From 2009 to 2019, 48 patients underwent reintervention for post-repair recoarctation in Shanghai Children’s Medical Center. Of the 48 patients, 22 patients had surgical repair, 25 patients had balloon angioplasty (BA), and 1 patient had a stent implantation. The clinical data were analyzed, and the difference in time-to-event distribution between the surgical group and the BA group was determined by a log-rank test. Results    The median age at reintervention was 15.0 months (range, 3.0 months-15.1 years). The median weight at reintervention was 9.8 kg (range, 3.0-58.0 kg). The time to reintervention after initial repair was 12.5 months (range, 2.0 months-7.8 years). One patient (2.1%) died in hospital and 1 patient (2.1%) experienced arrhythmia after surgical repair. One late mortality (2.1%) occurred after surgical reintervention. One patient (2.1%) experienced aortic dissection after BA. No patient died after BA. Freedom from residual coarctation or new recurrences was 66.7%, 61.3%, and 56.9%, respectively, at 1, 2, and 5 years after reintervention. Freedom from residual coarctation or new recurrences was 90.0%, 81.8%, and 70.1%, respectively, at 1, 2, and 5 years after surgical repair. Freedom from residual coarctation or new recurrences was 52.0%, 48.0%, and 48.0%, respectively, at 1, 2, and 5 years after BA. Compared with BA, surgery-based reintervention had a lower incidence of residual coarctation or recurrences (χ2=4.400, P=0.036). Conclusion    Reintervention for recoarctation has favorable early outcomes. Compared with balloon angioplasty, surgical repair has a more lasting effect in relieving the recoarctation.

Objective:To explore the effect of combining functional electric stimulation (FES) with upper limb cycle training in rehabilitating upper limb motor function and ability in the activities of daily living after a stroke.Methods:Sixty hemiplegic stroke survivors were randomly divided into an experimental group and a control group. In addition to conventional rehabilitation therapy, the experimental group underwent 20 minutes of MOTOmed upper limb cycle training every day while receiving FES. The control group received only the 20 minutes of cycle training. Before and after 4 weeks, Brunnstrom staging was used to quantify hand and upper extremity functioning. The Fulg-Meyer assessment upper extremity scale (FMA-UE) and the modified Barthel index (MBI) were also used before the training and after 1, 2, 3 and 4 weeks of the treatments.Results:After 4 weeks of treatment, significant differences were observed in the average BS scores of both groups compared with before the intervention. The average hand and upper limb stages of the experimental group were significantly better than the control group′s averages. Significant improvement was also observed in the average FMA-UE and MBI scores of both groups after only one week, with significantly greater improvement in the experimental group.Conclusions:Supplementing upper limb cycle training with FES can significantly improve the upper limb motor function and ability in the activities of daily living of stroke survivors. It is more effective than the MOTOmed exercise alone.

Objective    To explore the experience of surgical repair for congenital aortic stenosis (AS) in our center. Methods    We retrospectively reviewed the clinical data of 145 children diagnosed with AS, who underwent aortic repair from 2008 to 2019, with or without aortic insufficiency (AI), including 104 males and 41 females with a median age of 2.9 (0.6, 7.8) years. The preoperative and intraoperative data, early and long-term valvular function, long-term survival rate and freedom from reoperation and aortic valve replacment (AVR) were analyzed. Results    There were 120 patients receiving commissurotomy, 15 valvuloplasty with extra pericardium patch, and 25 AVR. The mean follow-up time was 0.25-11.20 (4.2±2.8) years. Survival rate at 10 years was 92.3%. Freedom from reoperation and AVR was 63.2% and 60.4%respectively. Multivariate analysis revealed that using a patch during surgery (P=0.036) was an independent risk factor for reoperation. A history of preoperative balloon dilation (P=0.029) and significant preoperative AI (P=0.001) contributed to AVR. Conclusion    Surgical treatment of congenital aortic valve stenosis in children is a safe and effective method that provides enough time to achieve a more definitive solution. Using a patch during surgery increases reoperation hazard. A history of previous balloon dilation and significant preoperative AI may result in AVR during the follow-up.

Objective    To investigate the prognosis and risk factors of mild to moderate or moderate atrioventricular valve regurgitation (AVVR) after Fontan operation. Methods    A total of 34 patients with mild to moderate or moderate AVVR who accepted Fontan operation and atrioventricular valve (AVV) repair between 2004 and 2018 in our center were selected as an AVV repair group. The patients in the same period were matched as a control group by the ratio of 1 : 1-2. Finally 99 patients were included into this study, including 64 males and 35 females, with an average age of 63.4±36.3 months and weight of 17.3±6.7 kg. Grades of AVVR decreased more than 1 was defined as significant improvement. Endpoints of the study were death, Fontan takedown, AVV replacement. Risk factors including Fontan procedures, AVV repair procedures, cardiac anatomy were analyzed. Results    Patients were followed up for 1.5 (0.3-4.0) years. Overall mortality was 15.2%. Most (82.4%) of AVV repair group accepted single AVV repair procedure while partial annuloplasty was the most common (52.9%). With the extension of follow-up, the degree of AVVR in the whole group showed a gradually increasing trend (r=0.352, P=0.000). Mild to moderate AVVR improved spontaneously after Fontan operation, while moderate AVVR did not. AVV repair could improve the degree of AVVR after moderate regurgitation, without increasing the surgical mortality, and regurgitation significantly decreased in 8.8% patients. AVV repair was not effective for mild to moderate AVVR and would increase surgical mortality. Conclusion    AVV function shows a gradual downward trend after Fontan operation. AVV repair is effective for moderate AVVR, does not increase mortality, but the degree of improvement is limited. AVV repair is not effective for mild to moderate AVVR and increases surgical mortality.

Objective To evaluate the effect of microvascular invasion (MVI) on prognosis of recipients after liver transplantation for primary liver cancer (liver cancer). Methods Clinical data of 177 recipients after liver transplantation for liver cancer were retrospectively analyzed. All patients were divided into the MVI-positive group (n=64) and MVI-negative group (n=113) according to postoperative pathological examination results. Clinical data were statistically compared of all recipients between the negative and positive MVI groups. The prognosis and risk factors of liver transplantation recipients for liver cancer were analyzed. Results Among 177 recipients, 64 cases (36.2%) were positive for MVI and 113 (63.8%) negative for MVI. Compared with the MVI-negative recipients, MVI-positive recipients had significantly lower degree of tumor differentiation, higher preoperative alpha-fetaprotein (AFP) level, larger maximal tumor diameter, a larger quantity of tumors, more satellite lesions and more recipients who did not meet the Milan criteria (all P < 0.05). The 1-, 3- and 5-year overall survival (OS) and recurrence-free survival (RFS) of recipients after liver transplantation for liver cancer were 80.2%, 62.1%, 58.5% and 66.3%, 57.5%, 51.2%, respectively. The 1-, 3- and 5-year OS and RFS of MVI-positive recipients were 70%, 39%, 35% and 53%, 39%, 33%, significantly lower than 86%, 75%, 72% and 73%, 68%, 63% of their counterparts negative for MVI (all P < 0.05). Cox regression analysis showed that the maximal tumor diameter >8 cm, preoperative AFP level ≥20 ng/mL, low degree of tumor differentiation and positive MVI were the independent risk factors for OS of recipients after liver transplantation for liver cancer (all P < 0.05). Positive MVI, low degree of tumor differentiation and preoperative down-staging failure were the independent risk factors for RFS of recipients after liver transplantation for liver cancer (all P < 0.05). Conclusions MVI is of significant clinical value in predicting clinical prognosis of recipients after liver transplantation for liver cancer.