Metastatic triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the accumulation of immunosuppressive cells. Herein, we designed a lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein (LV-sHDL) for combinational immunochemotherapy of metastatic TNBC. The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection. The multitargeted tyrosine kinase inhibitor (TKI) lenvatinib induced immunogenic cell death of the cancer cells, and the stimulator of interferon genes (STING) agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation, which synergistically improved the intratumoral infiltration of total and active CTLs by 33- and 13-fold, respectively. LV-sHDL inhibited the growth of orthotopic 4T1 tumors, reduced pulmonary metastasis, and prolonged the survival of animals. The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.

ObjectiveTo investigate the influencing factors for the short-term prognosis of patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). MethodsClinical data were collected from 240 HBV-ACLF patients without liver transplantation who were admitted To The Second Affiliated Hospital of Xi’an Jiaotong University from January 2009 to December 2019, and the patients were divided into groups according to survival on days 28 and 90 after admission (28-day survival group with 164 patients and 28-day death group with 76 patients; 90-day survival group with 140 patients and 90-day death group with 100 patients). The data collected included predisposing factors, liver function parameters, Model for End-Stage Liver Disease (MELD) score, MELD combined with serum sodium concentration (MELD-Na) score, and complications. The Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was plotted to calculate the area under the ROC curve (AUC), and a multivariate logistic regression analysis was used to investigate the risk factors for the short-term prognosis of HBV-ACLF. ResultsThe main predisposing factors of HBV-ACLF included spontaneous activation of HBV (55.6%) and HBV activation caused by the withdrawal of or resistance to nucleoside analogues (25.2%). There were significant differences in age, prothrombin time activity (PTA), neutrophil-lymphocyte ratio (NLR), serum sodium, MELD score, MELD-Na score, and total bilirubin (TBil) at baseline between the 28-day survival group and the 28-day death group (Z=-2.400,-6.015, -5.070, -5.103, -5.044, -7.430, and -6.637, all P＜0.05), and there were also significant differences in age, PTA, NLR, serum sodium, MELD score, MELD-Na, TBil, and cholesterol at baseline between the 90-day survival group and the 90-day death group (Z=-2.205, -7.728, -3.335, -4.015, -6.053, -7.908, -6.655, and -3.607, all P＜0.05). The multivariate logistic regression analysis showed that TBil ＞260.20 mmol/L (odds ratio ［OR］=4.572, 95% confidence interval ［CI］: 1.321-15823, P＜0.05), PTA ＜24.8% (OR=8.934, 95%CI: 3.026-26.374, P＜0.05), NLR＞5.63 (OR=2.632, 95%CI: 1.126-6.152, P＜0.05), serum sodium ＜130.8 mmol/L (OR=27.467, 95%CI: 6.113-123.423, P＜0.05), MELD score ＞17.84 (OR=4.303, 95%CI: 1.048-17.663, P＜0.05), and MELD-Na score ＞25.1 (OR=3.453, 95%CI: 1.614-7.387, P＜0.05) were independent risk factors for 28-day survival; TBil＞260.20 mmol/L (OR=5.148, 95%CI: 1.918-13.822, P＜0.05), PTA ＜25.5% (OR=15.718, 95%CI: 5.161-47.866, P＜0.05), serum sodium ＜135.3 mmol/L (OR=10.080, 95%CI: 3.244-31.323, P＜005), MELD score ＞17.84 (OR=11.157, 95%CI: 2.580-48.254, P＜0.05), MELD-Na score ＞25.1 (OR=4.391, 95%CI: 2057-9.372, P＜0.05) were independent risk factors for 90-day survival. Among the 240 patients, 160 (66.7%) experienced infection within 90 days, among whom 140 had bacterial infection, 12 had viral infection, and 8 had fungal infection. The 160 patients with infection had a significantly higher 90-day mortality rate than the patients without infection (46.3% vs 32.5%, χ2=6.720, P=0.010). Of all 240 patients, 176 had ascites, 44 had pleural effusion, 36 had acute renal injury, 60 had hepatic encephalopathy, and 12 had gastrointestinal bleeding within 28 days, and there were significant differences in the proportion of patients with acute renal injury, grade Ⅲ-Ⅳ hepatic encephalopathy, or gastrointestinal bleeding between the 28-day survival group and the 28-day death group (χ2=64.088，29811，7.797，all P＜0.05). ConclusionTBil, PTA, serum sodium, MELD score, and MELD-Na score at baseline are independent risk factors for the 28- and 90-day prognosis of HBV-ACLF. Liver inflammation and necrosis caused by HBV activation may be the initiating factor for ACLF, and infection, acute renal injury, hepatic encephalopathy, and gastrointestinal bleeding are the main complications affecting the prognosis of patients.

Chemotherapy is among the limited choices approved for the treatment of hepatocellular carcinoma (HCC) at intermediate and advanced stages. Preferential and prolonged drug exposure in diseased sites is required to maximize the therapeutic index of the drug. Here, we report an injectable supramolecular peptide hydrogel as an intraperitoneal depot for localized and sustained release of triptolide for the treatment of orthotopic HCC. We chose peptide amphiphile C-GNNQQNYKD-OH-based nanofibers as gelators and carriers for triptolide. Sustained triptolide release from the hydrogel was achieved over 14 days , with higher accumulation in and cytotoxicity against human HCC Bel-7402 in comparison with L-02 fetal hepatocytes. After intraperitoneal injection, the hydrogel showed prolonged retention over 13 days and preferential accumulation in the liver, realizing HCC growth inhibition by 99.7 ± 0.1% and animal median survival extension from 19 to 43 days, without causing noticeable pathological changes in the major organs. These results demonstrate that injectable peptide hydrogel can be a potential carrier for localized chemotherapy of HCC.

Objective To summarize the nursing methods for patients with hemophilia pseudotumor in coagulation factor replacement therapy during perioperative period. Methods A retrospective analysis was conducted among 25 hemophilia pseudotumor patients who were in the Orthopedic Department of Peking Union Medical College Hospital from June 2010 to September 2016, which were selected by convenience sampling method. All the patients were assessed for psychological status in a standardized method throughout the whole process and given timely intervention. The precise management of preoperative coagulation factor pretest, venous protection, observation and nursing of postoperative wound bleeding, monitoring and nursing of coagulation factor inhibitors were standardized using "Coagulation Factor Replacement Treatment Pre-experiment Information Record Table". Results All patients received accurate coagulation factor replacement therapy in perioperative period, which ensured the safety of perioperative period. In addition, all patients were discharged smoothly with an average hospitalization duration of 40.5 days. Conclusions Coagulation factor replacement therapy is the foundation to ensure patient safety, the key of which is accurate nursing. This study provides clinical practice experience for related nursing in China, and lays the foundation for further in-depth research in the future.

Objective: To explore the prognostic value of CD34, CD2, CD56 expressions and FLT3-ITD mutation in adults with acute promyelocytic leukemia (APL) . Methods: The immuno-phenotypic and molecular characteristics of 137 adult patients with APL (from January 2010 to March 2016, in Henan Provincial People’s Hospital) were investigated. And the relationships between CD34, CD2, CD56 expressions, FLT3-ITD mutation and the outcomes of high WBC counts at onset, complete remission (CR) rate, early mortality, relapse rate (RR) , overall survival (OS) , disease free survival (DFS) were explored. Results: ①Among the 137 patients, the positive ratios of CD34, CD2, CD56 expressions and mutation rate of FLT3-ITD were 26.3%, 25.5%, 10.2% and 17.5%, respectively. The morbidities of positive CD34, CD2, CD56 expressions and FLT3-ITD mutation in the high-risk group were 43.2%, 47.7%, 18.2% and 27.3% respectively, while those in the low-/intermediate-risk groups were 18.3%, 15.1%, 6.5% and 12.9%, respectively (P<0.05) . ②At a median follow-up of 41 months, the total CR rate of the 137 adults APL patients was 96.9%, early mortality 6.6% and relapse rate 7.3% respectively. And RR of positive CD34 or CD2 expression patients was higher than negative CD34/CD2 expression ones (18.8% vs 3.3%, χ²=8.462, P=0.004; 16.1% vs 4.3%, χ²=4.382, P=0.028, respectively) . In addition, the early mortality of patients with positive CD56 expression or FLT3-ITD mutation was extremely higher than in negative ones (21.4% vs 4.9%, χ²=5.610, P=0.018; 16.7% vs 4.4%, χ²=4.833, P=0.028, respectively) . ③The whole OS and DFS were 88.3% and 84.7%, respectively. Wherein, OS and DFS in patients with CD34⁺, CD56⁺ or FLT3-ITD mutation were worse (P<0.05) . Conclusions Positive CD34, CD2, CD56 expression and FLT3-ITD mutation were latent poor prognostic factors in adults with APL.

OBJECTIVETo explore the feature of primary light chain amyloidosis patients treated with high-dose melphalan with auto peripheral blood stem cell transplantation (auto-PBSCT) and bortezomib plus dexamethasone (VD).

METHODSThirty-eight patients diagnosed from September 2004 to September 2012 were analyzed retrospectively, including 15 cases received auto-PBSCT, 23 cases exposed with VD.

RESULTSThe median follow-up duration for the patients was 34 months (range, 1-112 months), including auto-PBSCT group of 38 months (range, 5-112 months) and VD group of 31 months (range, 1-108 months). The organ response rate in all the patients was 39.5% (15/38), and the organ response rate between these two groups has no significant difference [33.3% (5/15) vs 43.5% (10/23), P=0.532]. However, the median time of organ response was significant difference [6 (3-10) months vs 3 (1-6) months, respectively (P=0.032)]. The 3-year overall survival (OS) rates in the two groups were 72.0% and 66.9%, and their average survival were 84.7 months and 75.9 months, respectively (P=0.683). In the patients with auto-PBSCT, the occurrence of III-IV grade of bone marrow suppression (P<0.001), fever (P<0.001), nausea and infection (P=0.006) were obviously higher than those with VD, but there was no statistically significant difference in pulmonary infection (P=0.069) and bloodstream infection (P=0.059).

CONCLUSIONSThe preliminary results have presented that primary light chain amyloidosis patients treated with auto-PBSCT or VD had similar organ response rate and survival. However, more adverse events occurred in the group of auto-PBSCT.

Amyloidosis ; therapy ; Bortezomib ; therapeutic use ; Dexamethasone ; therapeutic use ; Humans ; Immunoglobulin Light-chain Amyloidosis ; Melphalan ; therapeutic use ; Myeloablative Agonists ; therapeutic use ; Peripheral Blood Stem Cell Transplantation ; Retrospective Studies

Humans ; Immunophenotyping ; Leukemia, Large Granular Lymphocytic ; classification ; complications ; Receptors, Antigen, T-Cell, gamma-delta ; beta-Thalassemia ; complications

Objective To introduce the laboratory and clinical characteristics of acute lymphoblastic leukemia accompanied by the karyotypic abnormality of 5q-.Methods Report the diagnosis and treatment of one case of acute lymphoblastic leukemia with 5q- and review the relevant literatures.Results The patient came to the hospital because of bellyache and ostalgia.The blood routine showed a high WBC count and reduced platelets.Bone marrow aspirates examination indicated acute leukemia and by peroxidase staining and flow cytometry test,acute pro-T lymphoblastic leukemia was diagnosed.The karyotype and fluorescence in situ hybridization analysis showed 5q-.The hyper-CVAD regimen induced a temporary remission but it did not work anymore after the relapse nor did the MEA regimen.From the literatures ever reported,the kyryotypic abnormality of 5q- was rarely seen in acute lymphoblastic leukemia.In such cases,the minimal deletion region overlaped between marks of D5S410 and D5S436 corresponding to chromosomal location 5q31-33.Conclusion 5q- is rare in acute lymphoblastic leukemia and more features are still to be found about the kind of disorder.

ObjectiveTo study the distribution,location and hemodynamics of perforating branches of the ulnar artery with color Doppler flow imaging (CDFI).MethodsPerforating branches of ulnar arteries were examined in 80 healthy volunteers in both forearms using CDFI.Following parameters were detected:number,diameter,jumping-off point,course,location and peak blood velocity.All the parameters data were analyzed statistically.ResultsThree hundred and forty-five perforating branches were detected in total 160ulnar arteries.These branches were classified into three types:type Ⅰ,myocutaneous perforator (10.3 ％);type Ⅱ,septocutaneous perforator(87 ％ ) ; type Ⅲ,direct cutaneous perforator (2.7 ％ ).The most dominant branches were located in the mesial of the upper third,middle third and lower third of the forearm.There was no significant difference among all age groups and no difference in peak blood velocity between left side and right side( P ＞0.05).The peak blood velocity was higher in male than that in female.( P ＜0.05).In relaxing period,the blood flow rate was almost disappeared and the frequency spectrum showed the characteristics of single direction,lower blood velocity and higher blood resistance.ConclusionsCDFI with high resolution showed better results of distribution and location of perforating branches of the ulnar artery and a better quality evaluation of the these branches.CDFI was helpful to design the skin flap containing cutaneous perforators of ulnar artery.

Objective To evaluate the diagnostic and therapeutic significance of serum free light chain (sFLC) in primary systemic(AL) amyloidosis. Methods Twenty-five patients with AL amyloidosis,including 18 men and 7 women with a mean age of 54(47-77) years old, were enrolled from October, 2005to May, 2010. sFLC was measured by immunoturbidimetric assay. The type of monoclonal light chain was judged upon sFLC κ/λ and its sensibility was compared with serum immunofixation and immunohistochemical analysis. Four patients were treated with M (T)D (melphalan/thalidomideand, dexamethasone), one with VD (velcade and dexamethasone) and four with high-dose melphalan followed by autologous stem cell support. The changes of sFLC were serially determined before and after treatment. Results Among the 25 patients with AL amyloidosis, two were κ light chains of precursor protein and 23 were λ light chains. Mean plasma cell in bone marrow was 3.5% (0-15%). Nineteen (76%) patients had abnormal elevated sFLC and abnormal κ/λ ratios, and 17(68% ) patients with immunofixation positive. The sFLC test had similar sensitivity as serum immunofixation (P = 0. 727 ). Twenty-one (84%) patients were shown to have either κor λ immunoreactive amyloid deposits on biopsied tissues. The sFLC test combined with serum immunofixation allowed the M protein to be detected in 22 (88%) patients. The positive rates of immunohistochemical analysis combined with sFLC test and/or serum immunofixation were 96%. Four patients with hematologic response showed obvious improvement in visceral organ involvement, but illness of 5 patients without hematologic response kept stable or progressed. Conclusions sFLC test is a sensitive qualitative and quantitative method to detect M protein. Preliminary data show the patients with obvious sFLC level decrease and/or κ/λ recovery to normal may have a high percentage of improved organs function. sFLC is critical index in diagnosing AL amyloidosis, which might help efficacy assessment.