Legionella effector LnaB is a phosphoryl AMPylase that impairs phosphosignalling.

AMPylation is a post-translational modification in which AMP is added to the amino acid side chains of proteins1,2. Here we show that, with ATP as the ligand and actin as the host activator, the effector protein LnaB of Legionella pneumophila exhibits AMPylase activity towards the phosphoryl group of phosphoribose on PRR42-Ub that is generated by the SidE family of effectors, and deubiquitinases DupA and DupB in an E1- and E2-independent ubiquitination process3-7. The product of LnaB is further hydrolysed by an ADP-ribosylhydrolase, MavL, to Ub, thereby preventing the accumulation of PRR42-Ub and ADPRR42-Ub and protecting canonical ubiquitination in host cells. LnaB represents a large family of AMPylases that adopt a common structural fold, distinct from those of the previously known AMPylases, and LnaB homologues are found in more than 20 species of bacterial pathogens. Moreover, LnaB also exhibits robust phosphoryl AMPylase activity towards phosphorylated residues and produces unique ADPylation modifications in proteins. During infection, LnaB AMPylates the conserved phosphorylated tyrosine residues in the activation loop of the Src family of kinases8,9, which dampens downstream phosphorylation signalling in the host. Structural studies reveal the actin-dependent activation and catalytic mechanisms of the LnaB family of AMPylases. This study identifies, to our knowledge, an unprecedented molecular regulation mechanism in bacterial pathogenesis and protein phosphorylation.

Nomogram predicts survival and surgical benefits for patients with breast cancer with initial bone metastasis: A population-based study.

BACKGROUND: Primary stage IV breast cancer is associated with a poor prognosis. At present, the value of local surgical treatment for patients with stage IV breast cancer remains uncertain; therefore, treatment principles remain controversial. Because of the high heterogeneity of these patients, it is often difficult to evaluate their prognoses. As a result, this study aimed to establish a prognostic nomogram to evaluate the prognosis of patients with breast cancer experiencing primary bone metastasis. METHODS: The clinical characteristics and follow-up data of patients with primary breast cancer and bone metastasis from 2010 to 2018 were collected from the Surveillance, Epidemiology, and End Results database and from 2013 to 2021 at the Peking Union Medical College Hospital. Patients were divided into training and validation groups. Multivariate Cox regression analysis was used to identify the independent prognostic variables for predicting cancer-specific survival (CSS). On the basis of these independent risk factors, a nomogram was developed and used calibration curves to evaluate its accuracy. Patients were divided into three risk groups according to their scores and surgery-related survival curves plotted using the log-rank test. RESULTS: Overall, 6372 patients were included, with 6319 from the Surveillance, Epidemiology, and End Results database and 53 from the Peking Union Medical College Hospital Breast Surgery Department. Multivariate analysis showed that age, race, marital status, grade, tumor stage, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status, and burden of other metastatic lesions were all associated with CSS. Based on these results, a nomogram that predicted the 1-, 3-, and 5-year CSS rates in patients with primary breast cancer and bone metastasis (concordance index > 0.69) was developed. After dividing patients into low-risk, high-risk, or super-high-risk groups based on nomogram scoring criteria, survival analysis revealed that patients in the low- and high-risk groups had significant survival benefits from primary focal surgery. CONCLUSION: Independent risk factors for primary breast cancer in patients with bone metastasis were analyzed and a nomogram established to predict CSS. The prognostic tool derived in this study can assist clinicians in predicting the survival and surgical benefits of these patients through scoring, thereby providing further guidance for treatment strategies.

Pedigree analysis exploring the inconsistency between diverse phenotypes and testing criteria for germline TP53 mutations in Chinese women with breast cancer.

PURPOSE: In the present study, we addressed the inconsistency between the testing criteria and diverse phenotypes for germline TP53 mutation in patients with breast cancer in the Chinese population. METHOD: We proposed a new added item (synchronous or metachronous bilateral breast cancer) as one of the testing criteria (aimed at high-penetrance breast cancer susceptibility genes) and applied it for determining TP53 germline mutation status in 420 female patients with breast cancer using multigene panel-based next-generation sequencing, Sanger sequencing, and mass spectrometry. RESULTS: We found that 1.4% of patients carried a pathogenic or likely pathogenic germline TP53 mutation. Compared with BRCA mutation carriers (8.0%) and non-carriers (7.1%), TP53 mutation carriers (33.3%) developed breast cancer earlier. The majority of TP53 mutation carriers (66.7%) developed breast cancer after age 30 and had bilateral breast cancer (33.3%). Pedigree investigation of four TP53 carriers and a patient with a TP53 variant of unknown significance revealed that neither of their parents harbored the same mutations as the probands, indicating that the mutations might occur de novo. CONCLUSION: Our study revealed distinguishing features of TP53 carriers among Chinese women with breast cancer, which is inconsistent with the currently used testing criteria; therefore, the newly proposed testing criteria may be more appropriate.

Rationale and design of a single-center randomized trial to compare the graft patency between the radial artery and the no-touch saphenous vein in coronary artery bypass grafting surgery (GRAFT-CAB Study).

BACKGROUND: Previous studies suggested only the radial artery and the No-touch (NT) technique were effective in reducing graft occlusion after coronary artery bypass grafting (CABG) surgery. However, there is no randomized trial comparing these 2 graft conduits. The optimum second conduit for CABG remains undetermined. MATERIALS AND METHODS: This study is a prospective, single-center randomized clinical trial, aiming to compare the graft patency between the radial artery and the NT vein graft. All patients undergoing isolated CABG with left internal mammary artery (LIMA) plus at least 2 additional grafts will be considered eligible. About 774 cases (516 in the radial artery group and 258 in the NT vein group) will be enrolled in over 1 to 2 years. Participants will be randomized and allocated to two bypass strategies: the LIMA plus 1 radial artery and 1 conventional vein graft, or the LIMA plus 2 NT vein grafts. The primary outcome is graft occlusion at 1 year after CABG evaluated by CT angiography. The secondary outcomes include graft occlusion at 3 and 5 years and major adverse cardiac or cerebrovascular events at 1, 3, and 5 years follow-ups. DISCUSSION: This study will define whether or not the NT vein has a lower graft occlusion rate than the radial artery in short and mid-term follow-ups, and provide new evidence for the second conduit choice in CABG surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT06014047. Registered on October 15th, 2023.

Nomogram prediction of the 70-gene signature (MammaPrint) binary and quartile categorized risk using medical history, imaging features and clinicopathological data among Chinese breast cancer patients.

BACKGROUND: The 70-gene signature (70-GS, MammaPrint) test has been recommended by the main guidelines to evaluate prognosis and chemotherapy benefit of hormonal receptor positive human epidermal receptor 2 negative (HR + /Her2-) early breast cancer (BC). However, this expensive assay is not always accessible and affordable worldwide. Based on our previous study, we established nomogram models to predict the binary and quartile categorized risk of 70-GS. METHODS: We retrospectively analyzed a consecutive cohort of 150 female patients with HR + /Her2- BC and eligible 70-GS test. Comparison of 40 parameters including the patients' medical history risk factors, imaging features and clinicopathological characteristics was performed between patients with high risk (N = 62) and low risk (N = 88) of 70-GS test, whereas risk calculations from established models including Clinical Treatment Score Post-5 years (CTS5), Immunohistochemistry 3 (IHC3) and Nottingham Prognostic Index (NPI) were also compared between high vs low binary risk of 70-GS and among ultra-high (N = 12), high (N = 50), low (N = 65) and ultra-low (N = 23) quartile categorized risk of 70-GS. The data of 150 patients were randomly split by 4:1 ratio with training set of 120 patients and testing set 30 patients. Univariate analyses and multivariate logistic regression were performed to establish the two nomogram models to predict the the binary and quartile categorized risk of 70-GS. RESULTS: Compared to 70-GS low-risk patients, the high-risk patients had significantly less cardiovascular co-morbidity (p = 0.034), more grade 3 BC (p = 0.006), lower progesterone receptor (PR) positive percentage (p = 0.007), more Ki67 high BC (≥ 20%, p < 0.001) and no significant differences in all the imaging parameters of ultrasound and mammogram. The IHC3 risk and the NPI calculated score significantly correlated with both the binary and quartile categorized 70-GS risk classifications (both p < 0.001). The area under curve (AUC) of receiver-operating curve (ROC) of nomogram for binary risk prediction were 0.826 (C-index 0.903, 0.799-1.000) for training and 0.737 (C-index 0.785, 0.700-0.870) for validation dataset respectively. The AUC of ROC of nomogram for quartile risk prediction was 0.870 (C-index 0.854, 0.746-0.962) for training and 0.592 (C-index 0.769, 0.703-0.835) for testing set. The prediction accuracy of the nomogram for quartile categorized risk groups were 55.0% (likelihood ratio tests, p < 0.001) and 53.3% (p = 0.04) for training and validation, which more than double the baseline probability of 25%. CONCLUSIONS: To our knowledge, we are the first to establish easy-to-use nomograms to predict the individualized binary (high vs low) and the quartile categorized (ultra-high, high, low and ultra-low) risk classification of 70-GS test with fair performance, which might provide information for treatment choice for those who have no access to the 70-GS testing.

No-Touch Versus Conventional Vein Harvesting Techniques at 12 Months After Coronary Artery Bypass Grafting Surgery: Multicenter Randomized, Controlled Trial.

BACKGROUND: Vein graft occlusion is deemed a major challenge in coronary artery bypass grafting. Previous studies implied that the no-touch technique for vein graft harvesting could reduce occlusion rate compared with the conventional approach; however, evidence on the clinical benefit and generalizability of the no-touch technique is scare. METHODS: From April 2017 to June 2019, we randomly assigned 2655 patients undergoing coronary artery bypass grafting at 7 hospitals in a 1:1 ratio to receive no-touch technique or conventional approach for vein harvesting. The primary outcome was vein graft occlusion on computed tomography angiography at 3 months and the secondary outcomes included 12-month vein graft occlusion, recurrence of angina, and major adverse cardiac and cerebrovascular events. The generalized estimate equation model was used to account for the cluster effect of grafts from the same patient. RESULTS: During the follow-up, 2533 (96.0%) participants received computed tomography angiography at 3 months after coronary artery bypass grafting and 2434 (92.2%) received it at 12 months. The no-touch group had significantly lower rates of vein graft occlusion than the conventional group both at 3 months (2.8% versus 4.8%; odds ratio, 0.57 [95% CI, 0.41-0.80]; P<0.001) and 12 months (3.7% versus 6.5%; odds ratio, 0.56 [95% CI, 0.41-0.76]; P<0.001). Recurrence of angina was also less common in the no-touch group at 12 months (2.3% versus 4.1%; odds ratio, 0.55 [95% CI, 0.35-0.85]; P<0.01). Rates of major adverse cardiac and cerebrovascular events were of no significant difference between the 2 groups. The no-touch technique was associated with higher rates of leg wound surgical interventions at 3-month follow-up (10.3% versus 4.3%; odds ratio, 2.55 [95% CI, 1.85-3.52]; P<0.001). CONCLUSIONS: Compared with the conventional vein harvesting approach in coronary artery bypass grafting, the no-touch technique significantly reduced the risk of vein graft occlusion and improved patient prognosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03126409.

Long-term survival of screen-detected synchronous and metachronous bilateral non-palpable breast cancer among Chinese women: a hospital-based study (2003-2017).

PURPOSE: Screen-detected unilateral non-palpable breast cancer (NPBC) shows favorable prognosis, whereas bilateral breast cancer (BBC), especially synchronous BBC (SBBC) manifests worse survival than unilateral breast cancer (BC). It remains unclear whether screen-detected bilateral NPBC has compromised survival and requires intensified treatment or favorable prognosis and needs de-escalating therapy. METHODS: From 2003 to 2017, 1,075 consecutive NPBC patients were retrospectively reviewed. There were 988 patients with unilateral NPBC (UniNPBC), and 87 patients with ipsilateral NPBC + any contralateral BC [(N + AnyContra) PBC], including 32 patients with bilateral NPBC (BiNPBC) and 55 patients with ipsilateral NPBC + contralateral palpable cancer [(N + Contra) PBC]. Median follow-up time was 91 (48-227) months. Clinicopathological characteristics were compared between UniNPBC and BBC, whereas relapse-free survival (RFS) and overall survival (OS) among BBC subgroups. RFS and OS factors of BBC were identified. RESULTS: Compared to UniNPBC, patients with screen-detected bilateral BC had more invasive (85.1%, 74.8%), ER negative (26.4%, 17.1%), PR negative (36.8%, 23.5%), triple-negative (21.6%, 8.5%) BC as well as less breast conserving surgery (17.2%, 32.4%), radiotherapy (13.8%, 32.0%) and endocrine therapy (71.3%, 83.9%). 10 year RFS and OS rates of (N + AnyContra) PBC (72.8%, 81.5%), (N + Contra) PBC (60.6%, 73.9%), and synchronous (N + Contra) PBC (58.1%, 70.1%) were significantly compromised compared to UniNPBC (91.0%, 97.2%). RFS factors of BBC included pN3 (p = 0.048), lymphovascular invasion (p = 0.008) and existence of contralateral palpable interval BC (p = 0.008), while the OS relevant factor was pN3 (p = 0.018). CONCLUSION: Screen-detected bilateral NPBC including SynBiNPBC and MetaBiNPBC showed good prognosis as UniNPBC so that the therapy of BiNPBC could be de-escalated and optimized according to UniNPBC. Contrarily, screen-detected ipsilateral NPBC with contralateral palpable BC [(N + Contra) PBC] manifested unfavorable survival worse than UniNPBC and synchronous (N + Contra) PBC had the worst survival among all subgroups, implying that these were actually bilateral interval BC and required intensified treatment.

Rationale and design of a phase II trial of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for N0/N1mi, HER2 + early breast cancer (PHAEDRA).

BACKGROUND: The de-escalation treatment in patients with low-risk HER2-positive early breast cancer (eBC) is an attractive strategy to avoid unnecessary treatment and improve the quality of life of patients. Pyrotinib, a novel irreversible pan-HER2 tyrosine kinase inhibitor (TKI), has shown efficacy in patients with advanced HER2-positive breast cancer. Meanwhile, nanoparticle albumin-bound (nab)-paclitaxel reveals survival benefit over solvent-based paclitaxel and eliminates the toxicities associated with the solvent. However, the efficacy and safety of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for low-risk HER2 + eBC patients have not been evaluated. METHODS: This is a multicenter, open-label, single-arm phase II study. A sample size of 261 patients with tumor ≤ 3 cm, lymph node-negative (N0) or micrometastatic (N1mi), HER2 + breast cancer will be recruited. Eligible patients will receive nab-paclitaxel 260 mg/m2 once every 3 weeks for 12 weeks and pyrotinib 400 mg once daily for one year. The primary endpoint is invasive disease-free survival. A sub-study will be conducted to investigate different prophylactic strategies for diarrhea, which is the most common adverse event of pan-HER TKIs. One hundred and twenty patients from the main study will be randomly (1:1) allocated to receive loperamide either during the first cycle (4 mg tid on days 1-7, then 4 mg bid on days 8-21) or the first 2 cycles (4 mg tid on days 1-7, then 4 mg bid on days 8-42). The primary endpoint of the sub-study is the incidence of grade ≥ 3 diarrhea. DISCUSSION: This is the first prospective study of pyrotinib in combination with nab-paclitaxel as adjuvant therapy for patients with low-risk HER2-positive eBC. It would probably provide robust evidence for de-escalating strategy of HER2-positive eBC and appropriate management for pyrotinib-related diarrhea. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04659499 . Registered on December 9, 2020.

Dynamic change of serum CA19-9 levels in benign and malignant patients with obstructive jaundice after biliary drainage and new correction formulas.

BACKGROUND: CA19-9 is one of the most widely used tumor markers in biliary-pancreatic diseases. The measured value may not factually reflect the genuine CA19-9 level secreted by tumor, which affected by biliary obstruction. There is an urgent need of developing a correction formula of CA19-9 in biliary obstructive patients to guide clinical practice and avoid making improper clinical decision. METHODS: Clinical characteristics were collected among patients undergoing biliary drainage in our hospital between January 2014 and January 2019. By comparing the malignant and benign patients statistically, dynamic change trend of CA19-9 levels after biliary drainage was obtained. The correction formulas of CA19-9 were generated by means of linear regression. RESULTS: 121 patients, including 102 malignant and 19 benign patients, were enrolled in this study. The baseline CA19-9 level of malignant patients is much higher than that of benign patients. Total bilirubin (TB) level was found to be not related with CA19-9 value (p = 0.109). The drop proportion of the average CA19-9 level in the malignant patients (39.2%, IQR -18.4-78.6%) was much lower than that in the benign patients (75.7%, IQR 58.1-86.6%) (p = 0.014). The correction formula, CA19-9True = 0.63 × CA19-9Measured - 20.3 (R2 = 0.693, p<0.001), was generated based on the linear relation between CA19-9 after drainage and CA19-9 before drainage in malignant patients, which had similar diagnostic value with true CA19-9 value. CONCLUSIONS: Quantitative correction formulas of CA19-9 considering the effect of biliary decompression was first proposed in this study, aiming to provide a more accurate CA19-9 level to make more accurate clinical decision and avoid making improper therapeutic schedule.

The clinical features and prognosis of patients with mucinous breast carcinoma compared with those with infiltrating ductal carcinoma: a population-based study.

BACKGROUND: At present, the characteristics of mucinous breast carcinoma (MBC) and the factors affecting its prognosis are controversial. We compared the clinical features of MBC with those of infiltrating ductal carcinoma (IDC) and summarized the relevant prognostic factors. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database includes information on 10,593 patients diagnosed with MBC between 2004 and 2016. Chi-square tests and analyses were used to analyze differences in variables between the MBC and IDC groups. Univariate and multivariate Cox proportional hazards models were used to assess the relative impacts of risk factors on cancer-specific survival (CSS) in patients. Kaplan-Meier survival curves were constructed to assess cancer-specific mortality and were compared using the log-rank test. RESULTS: From 2004 to 2016, 10,593 people were diagnosed with MBC, and 402,797 were diagnosed with IDC. Patients with MBC had significantly higher 5-/10-year CSS rates (96.4%/93.4%) than those with IDC (89%/83.8%). Compared with IDC patients, MBC patients had less lymph node metastasis, an earlier stage, a higher rate of hormone receptor positivity and a lower expression rate of HER2. Univariate and multivariate analyses showed that age ≥ 60 years old (HR = 1.574, 95%CI: 1.238-2.001, P < 0.001), singled status (HR = 1.676, 95%CI: 1.330-2.112, P < 0.001) and advanced TNM/SEER stage were independent prognostic risk factors for MBC. In addition, positive estrogen receptor (HR = 0.577, 95%CI: 0.334-0.997, P = 0.049), positive progesterone receptor (HR = 0.740, 95%CI: 0.552-0.992, P = 0.044), surgical treatment (HR = 0.395, 95%CI: 0.288-0.542, P < 0.001) and radiotherapy (HR = 0.589, 95%CI: 0.459-0.756, P < 0.001) were identified as protective factors. CONCLUSION: Compared with IDC, MBC has a better prognosis. For patients with MBC, we identified prognostic factors that can help clinicians better assess patient outcomes and guide individualized treatment.

Nomograms predict survival of patients with small bowel adenocarcinoma: a SEER-based study.

BACKGROUND AND OBJECTIVE: Small bowel adenocarcinoma (SBA) is a rare malignant tumor with a poor prognosis. Most patients with SBA are diagnosed with advanced-stage disease. Due to the lack of randomized controlled trials and prospective studies, it is difficult to predict the prognosis of patients with SBA. Thus, this study aimed to establish a prognostic nomogram for evaluating the prognosis of SBA patients. METHODS: The clinical features and follow-up data of all patients diagnosed with SBA during 2004-2016 were summarized from the Surveillance, Epidemiology, and End Results (SEER) database. We separated these patients into training and validation groups. Multivariate Cox regression analyses were performed to identify independent prognostic variables for predicting cancer-specific survival (CSS) and overall survival (OS). According to the independent risk factors, we established nomograms and used the calibration curves to evaluate the accuracy. RESULTS: The data of 3301 patients with SBA were collected from the SEER database. The multivariate analysis showed that age, marital status, tumor site, grade, TNM stage and surgical history were associated with CSS and OS (P < 0.05). Based on these results, we established nomograms of CSS and OS that can predict the 3- and 5-year survival rates of SBA patients (C-index > 0.7). The calibration curves showed that the predicted survival was very close to the actual survival. CONCLUSION: We analyzed the independent risk factors for prognosis of SBA patients, and established nomograms to predict the 3- and 5-year survival rates of OS and CSS. These new prognostic tools can help clinicians to predict the survival of patients with SBA, further to guide treatment strategy.

[Application Value of Abbreviated Comprehensive Geriatric Assessment in Elderly Female Breast Cancer Patients].

Objective To evaluate the application value of abbreviated comprehensive geriatric assessment(aCGA)in elderly female breast cancer patients. Methods Eight aspects of the traditional CGA were simplified to form the aCGA assessment table,based on which the patients were classified into three grades of A,B and C according to the total scores.This study enrolled the elderly female patients with breast cancer aged 70 years and above who were treated in PUMC Hospital from June 2018 to January 2020.Eastern Cooperative Oncology Group(ECOG)scoring and aCGA grading were performed respectively,and the results of the two methods were compared. Results Of the 162 patients,111(68.5%)were classified by the aGGA method as grade A,43(26.5%)as grade B,and 8(5.0%)as grade C;131(80.9%)cases have concurrent diseases,and the most common complications were hypertension(n=89),cardiovascular diseases(n=47)and diabetes mellitus(n=39).The ECOG score was 0-1 in 133(82.0%)cases,2 in 24(14.8%)cases and 3 in 5(3.2%)cases.The ECOG score showed 133(82.0%)cases with good status and 29 cases with poor status.However,according to the aCGA classification,111 cases were in good health status and 51 cases were in poor health status;the difference in the result between the two groups was statistically significant(χ 2=14.24,P<0.001).Conclusion Compared with ECOG score,aCGA grading can more comprehensively evaluate the health status of elderly female breast cancer patients and can be applied to the patients aged 70 and above.

Clinical characteristics and prognostic factors of Hurthle cell carcinoma: a population based study.

BACKGROUND: Thyroid Hurthle cell carcinoma (HCC) is a rare disease with high risk of invasion and metastasis and poor prognosis. The clinical characteristics, prognosis and treatment of HCC are still controversial, and clinical data are still limited to some case reports. Therefore, understanding the characteristics and survival factors of HCC is clinically necessary. METHODS: This study collected data from HCC patients diagnosed pathologically from 2004 to 2015, including basic population characteristics, tumor characteristics, and epidemiological and survival data. The data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to conduct a population cohort study. RESULTS: A total of 2101 HCC patients with an average age of 55.42 ± 15.27 years were enrolled in this study. Of them, 1740 (82.82%) patients had local disease, 245 (11.66%) had regional disease, and 89 (4.24%) had distant disease. Total thyroidectomy was performed in 1669 (79.44%) patients, partial thyroidectomy was performed in 382 (18.18%) patients, and radioactive iodine (RAI) was used in 1155 (54.97%) patients. The 5-year and 10-year cancer-specific survival rate was 95.4 and 92.6%, respectively. The distant disease group had significantly more male patients, multifocal tumors, and extensive tumors compared to the local disease group. Multivariate survival analysis showed that age (P < 0.05), SEER stage (P < 0.001), and T-stage (P = 0.001) had significant effects on survival. There was no significant difference in survival between total and partial thyroidectomy (P = 0.078), or between RAI and non-RAI (P = 0.733). CONCLUSION: Male gender, multifocal tumors, and extended tumors are associated with increased risk of late stage HCC. Age over 45 years, distant SEER stage, and late T-stage are independent risk factors for mortality in HCC.

Efficacy and safety of taxane plus anthracycline with or without cyclophosphamide in Chinese node-positive breast cancer patients: an open-label, randomized controlled trial.

PURPOSE: To evaluate and compare the efficacy and safety of the taxane plus anthracycline (TA) regimen vs. the taxane plus anthracycline plus cyclophosphamide (TAC) regimen as adjuvant chemotherapy in Chinese patients with node-positive breast cancer (BCa). METHODS: Patients with BCa (n = 640) were recruited between January 2010 and June 2012. All patients were randomized to receive six cycles of adjuvant therapy with the TA or TAC regimen. The primary endpoint was disease-free survival (DFS). The secondary endpoints were overall survival (OS), quality of life (QoL), and chemotherapy-related toxicity. Finally, 630 patients were evaluable, with a median follow-up of 70 months. RESULTS: There were no differences in the 70-month median DFS and OS between the two groups (DFS: TA 79.7% vs. TAC 75.6%, P = 0.371; OS: TA vs. TAC, 85.1% vs. 87.6%, P = 0.271). The TA group had lower frequencies grade III/IV vomiting (TA vs. TAC, 11.7% vs. 18.1%, P = 0.025) and nausea (13.0% vs. 19.4%, P = 0.031). The health-related QoL score was higher in the TA group (74.1 ± 5.3 vs. 67.9 ± 4.4, P = 0.001 vs. TAC). CONCLUSIONS: In the adjuvant setting, compared with the TAC regimen, the TA regimen exhibits no significant difference with respect to DFS and OS in Chinese patients with node-positive BCa. On the other hand, TA is associated with less severe adverse events, lower economic burden, and better QoL.

Duodenal descending part-jejunum intussusception and upper gastrointestinal bleeding caused by duodenal fibrolipoma: a case report.

BACKGROUND: Duodenal fibrolipoma and duodenum-jejunum intussusception are both rare occasions in clinical practice. The diagnosis of duodenal fibrolipoma mainly depends on endoscopy examination, supplemented by CT and MRI. As the tumor grows, some severe symptoms need surgical intervention. As the development of endoscopic techniques, the operation plan should be made individually. CASE PRESENTATION: A 47-year-old female with the complaint of upper abdominal pain and melena was reported. Abdominal examination revealed upper abdomen lightly tender and blood test showed severe anemia. Image and endoscopy examination exhibited "a giant mass" in the descending (D2) part of duodenum, dragged by the tumor into the distal intestinal canal and causing intussusception. Intermittent blood transfusion treatment, enteral and parenteral nutrition were adopted to adjust her general state. Two weeks later, the mass was resected together with the basement intestinal wall via the jejunum incision and then the intussuscepted D2 part was restored. The paraffin pathological diagnosis correlated with the preoperative judgment of fibrolipoma and the patient was discharged healthy on POD 14. CONCLUSIONS: Duodenal fibrolipoma is a rare disease, infrequently causing intussusception and severe upper GIB. Duodenoscopy and endoscopic ultrasound contribute to making an appropriate diagnosis, and for patients with severe symptoms needed surgical intervention, operation plan should be individualized depending on the size and location of the lesion.

Clinical Outcomes of Surgical Revascularization Strategies Guided by Quantitative Flow Ratio in Primary Noncoronary Cardiac Surgery.

PURPOSE: Information regarding quantitative flow ratio (QFR) usage in coronary artery bypass grafting (CABG) is lacking. We compared the incidence of postoperative long-term adverse cardiovascular and cerebrovascular events after QFR-guided or coronary angiography-guided adult cardiac surgery with concurrent bypass surgery. MATERIALS AND METHODS: This study included 432 patients who underwent cardiopulmonary bypass (CPB) at our institution with at least 1 angiographical coronary artery lesion (diameter stenosis: 30% to 90%) between January 2015 and January 2016. The QFR of each patient was calculated. Patients who only underwent intraoperative coronary revascularization following the principles of optimal revascularization strategy were assigned to group A. Patients with coronary lesions not meeting the above criteria were placed in group B. RESULTS: The average number of distal anastomoses of patients with combined CABG in group B was similar to that in Group A (1.9±1.0 vs. 1.7±0.9; P=0.081). Group A had a shorter CPB duration (114.4±49.2 vs 135.8±55.2 minutes; P<0.001) and shorter aortic cross-clamping time (83.6±36.2 vs 101.1±40.6 minutes; P<0.001). The rates of perioperative mortality and major complications did not differ between groups. Long-term major adverse cardiovascular and cerebrovascular events (MACCEs) were less common in group A than in group B (14.7% vs 29.5%; P<0.001). CONCLUSIONS: In primary noncoronary cardiac surgery, despite the similar average numbers of distal anastomoses, the group with target vessels treated using an optimal coronary revascularization strategy presented shorter CPB time and aortic cross-clamping time than the other group. Multivariate analyses also showed a lower incidence of long-term MACCEs.

IFIT1 modulates the proliferation, migration and invasion of pancreatic cancer cells via Wnt/ß-catenin signaling.

OBJECTIVES: Previously, Interferon-induced Protein with Tetratricopeptide Repeats 1 (IFIT1) has been shown to promote cancer development. Here, we aimed to explore the role of IFIT1 in the development and progression of pancreatic cancer, including the underlying mechanisms. METHODS: We explored IFIT1 expression in pancreatic cancer samples using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Cell Counting Kit-8 (CCK8), colony formation, scratch wound-healing and Transwell assays were performed to assess the proliferation, migration and invasion abilities of pancreatic cancer cells. Gene Set Enrichment Analysis (GSEA) and Western blotting were performed to assess the regulatory effect of IFIT1 on the Wnt/ß-catenin pathway. RESULTS: We found that upregulation of IFIT1 expression is common in pancreatic cancer and is negatively associated with overall patient survival. Knockdown of IFIT1 expression led to decreased proliferation, migration and invasion of pancreatic cancer cells. We also found that IFIT1 could regulate Wnt/ß-catenin signaling, and that a Wnt/ß-catenin agonist could reverse this effect. In addition, we found that IFIT1 can promote epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. CONCLUSIONS: Our data indicate that IFIT1 increases pancreatic cancer cell proliferation, migration and invasion by activating the Wnt/ß-catenin pathway. In addition, we found that EMT could be regulated by IFIT1. IFIT1 may serve as a potential therapeutic target for pancreatic cancer.

Long-term outcomes of a novel fully magnetically levitated ventricular assist device for the treatment of advanced heart failure in China.

PURPOSE: Left ventricular assist devices (LVADs) are well-established for treating end-stage heart failure, but this therapy is only available to Chinese patients in recent years. The CH-VAD is the first used fully magnetically levitated pump and the most widely used device in China. This study reports the long-term outcomes of a cohort supported by the CH-VAD for the first time. METHODS: From June 2017 to August 2023, 50 consecutive patients received CH-VAD implantation in Fuwai Hospital. Clinical data were collected during follow-up and retrospectively analyzed. RESULTS: Baseline characteristics included a mean age of 47.9±13.9 years, 90% male, and 26% ischemic etiology. The INTERMACS profile revealed 12% Profile 1, 56% Profile 2, 26% Profile 3 and 6% Profile 4. Mean support duration was 868 ± 630 days (range 33 days-6.4 years). Kaplan-Meier survival rate was 96% (95% confidence interval [CI], 85 to 99) at 6 months, 93% (95% CI, 79-98) at 1 year, 93% (95% CI, 79-98) at 2 years and 89% (95% CI, 71-96) at 3 years. 40 patients (80%) currently remain on support, 3 were bridged to recovery, 2 received transplant, and 5 expired during support. Major adverse events included right heart failure (10%), surgical related bleeding (8%), arrhythmia (8%) and driveline infection (16%). Major hemocompatibility-related adverse events were limited to 3 non-disabling strokes and 1 gastrointestinal bleeding. There was no major device malfunction during the follow-up period. CONCLUSIONS: The largest single-center experience with the leading LVAD in China shows high survival with low complication rates, demonstrating the CH-VAD is safe and efficient in providing long-term support for end-stage heart failure patients.

Surgical treatment of cardiac lipoma: 20 years' experience in a single center.

BACKGROUND: Primary cardiac lipoma is very rare, and no consensus has been developed regarding its ideal treatment strategy. This study reviewed the surgical treatment of cardiac lipomas in 20 patients over 20 years. METHODS: Twenty patients with cardiac lipomas were treated at Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2002, to January 1, 2022. The patients' clinical data and pathological reports were retrospectively analyzed, and the follow-up with a range of 1 year to 20 years was conducted. RESULTS: The cardiac lipomas were located in the right atrium (RA) or superior vena cava (SVC) in seven patients (35%) (RA in six patients and SVC in one patient), left ventricle in eight patients (40%) (left ventricular chamber in four patients and left ventricular subepicardium and myocardium in four patients), right ventricle in three patients (15%) (right ventricular chamber in one patient and right ventricular subepicardial layer and myocardium in two patients), subepicardial interventricular groove in one patient (5%), and pericardium in one patient (5%). Complete resection was achieved in 14 patients (70%), including seven patients with lipomas in the RA or SVC. Incomplete resection occurred in six patients (30%) with lipomas in the ventricles. No perioperative deaths occurred. Long-term follow-up was conducted for 19 patients (95%), including two (10%) who died. Both patients who died had lipomas incompletely resected due to ventricles involvement, and preoperative malignant arrhythmias persisted post-operatively. CONCLUSIONS: The complete resection rate was high, and the long-term prognosis was satisfactory in patients with cardiac lipomas that did not involve the ventricle. The complete resection rate was low in patients with cardiac lipomas in ventricles; and complications, including malignant arrhythmia, were common. Failure of complete resection and post-operative ventricular arrhythmia are correlated with post-operative mortality.

Considerable Long-Term Aesthetic Outcomes and Oncologic Safety of Breast-Conserving Surgery Via a Periareolar Incision: A Retrospective Study.

BACKGROUND: To investigate the application effect of periareolar incision breast-conserving surgery in patients with early breast cancer. METHODS: From January 2017 to November 2021, a clinician in our research center performed a total of 533 breast-conserving surgery. After screening, we collected the information of 209 patients through telephone, online questionnaires, and outpatient follow-up. One hundred seventeen patients with early breast cancer underwent breast-conserving surgery under the periareolar incision, while 92 patients underwent surgery through the tumor surface incision. We compared the differences between the 2 groups in the length of stay, postoperative complications, adjuvant therapy, and other clinical indicators, as well as the subjective and objective evaluation of the long-term postoperative breast aesthetic outcome, local recurrence, distant metastasis, and survival. RESULTS: With a mean follow-up of 3.9 years, patients in the periareolar incision group (PAIG) and tumor surface incision group (TSIG) had no significant differences in clinical indicators, local recurrence, distant metastasis, and survival. However, PAIG patients had better subjective satisfaction with postoperative breast appearance. In the evaluation of objective aesthetic outcomes, PAIG was significantly better than TSIG in texture and elasticity, symmetry, sunken degree of the operative side, skin color, surgical scar, and breast compliance difference. CONCLUSION: By observing and comparing the clinical indicators, postoperative recurrence, and metastasis of the enrolled patients, this study found that periareolar incision surgery could achieve radical therapeutic effects similar to those achieved through tumor surface incision, and had advantages in improving postoperative aesthetic outcomes, which could provide certain references for clinical practice.