In vivo near infrared fluorescence imaging and dynamic quantification of pancreatic metastatic tumors using folic acid conjugated biodegradable mesoporous silica nanoparticles

Cancer metastasis is one of the biggest challenges in cancer treatments since it increases the likelihood that a patient will die from the disease. Therefore, the availability of techniques for the early detection and quantification of tumors is very important. We have prepared cyanine 7.5 NHS ester (Cy_7.5) and folic acid (FA) conjugated biodegradable mesoporous silica nanoparticles (bMSN@Cy_7.5-FA NPs) (~100 nm) for visualizing tumors in vivo. The fluorescence spectra revealed that the emission peak of bMSN@Cy_7.5-FA NPs had a red-shift of 1 nm. Confocal immunofluorescent images showed that bMSN@Cy_7.5-FA NPs had an excellent targeting ability for visualizing cancer cells. In vivo fluorescence imaging has been conducted using an orthotopic model for pancreatic cancer within 48 h, and the fluorescence intensity reached a maximum at a post injection time-point of 12 h, which demonstrated that the use of bMSN@Cy_7.5-FA NPs provides an excellent imaging platform for tumor precision therapy in mice.     

Severe thrombocytopenia in pregnancy: a case series from west China

Thrombocytopenia is the second most common hematological disease during pregnancy and is mainly caused by gestational thrombocytopenia, immune thrombocytopenia, or preeclampsia/HELLP syndrome. This study aims to investigate the causes and pregnancy outcomes of thrombocytopenia in pregnancies with platelet counts below 50 × 10⁹/L. We retrospectively analyzed the pregnancies diagnosed with severe thrombocytopenia at a tertiary care center in western China between January 2009 and December 2017. All enrolled pregnancies were divided into three groups according to the lowest platelet counts: group A (30–50 × 10⁹/L), group B (10–30 × 10⁹/L), and group C (< 10 × 10⁹/L). Maternal and fetal outcomes were observed and compared among these three platelet levels. A total of 533 consecutive pregnancies were included. A relatively large proportion (37.3%, 199/533) of them showed a history of thrombocytopenia before pregnancy or during a previous pregnancy. Most of the women (70.2%, 374/533) received corticosteroids, intravenous immunoglobulin, or platelet transfusion treatments. The incidence of preterm birth < 37 weeks (26.3%, 15/57), cesarean section (93%, 53/57), and neonatal intensive care unit (NICU) admission (31.6%, 18/57) occurred significantly more often in group C than in groups A and B. Neonatal platelet counts were detected in 28.2% of the infants (155/549), and neonatal thrombocytopenia was found in 40.6% of the infants (63/155). Intracranial hemorrhage occurred in 0.9% of the neonates (5/549) throughout the study period, with neonatal nadir platelet counts between 20 × 10⁹/L and 245 × 10⁹/L. One perinatal death occurred in group C. Pregnancies with the lowest platelet counts below 10 × 10⁹/L are more often complicated by preterm birth, cesarean section, and NICU admission compared with those lowest platelet counts 30–50 × 10⁹/L and 10–30 × 10⁹/L. Neonatal intracranial hemorrhage was uncommon in pregnancies with severe thrombocytopenia. Active management should be performed to avoid possible preterm birth and neonatal NICU admission in pregnancies with the lowest platelet counts below 10 × 10⁹/L.

     

Mutation spectrum of MMACHC in Chinese pediatric patients with cobalamin C disease: A case series and literature review

Cobalamin (cbl) C disease is a rare autosomal recessive inheritance disease, which is the most common cobalamin metabolic disorder. Its clinical phenotype involves multiple systems with varying degrees of severity, where in mild cases can be asymptomatic for many years, whereas severe cases may cause death during the neonatal period. The disease is caused by mutations in the MMACHC gene located on chromosome 1p34.1 that contains 5 exons; among which, exons 1–4 have an 849 bp coding sequence that encodes a protein containing 282 amino acids. Through clinical physical examination and laboratory tests, especially blood and urine screening, we found 28 cblC pediatric patients with clinical manifestations, such as mental retardation, motor development delay, epilepsy, metabolic acidosis, vomiting and diarrhea. By Sanger sequencing, we found homozygous or compound heterozygous mutations of MMACHC in 27 of the patients, and single heterozygous mutation of MMACHC in one of them. The c.609G > A, c.658-660delAAG, c.80A > G and c.482G > A mutations accounted for 43.64% (24/55), 10.91% (6/55), 9.09% (5/55) and 7.27% (4/55) of all the mutations, respectively. This spectrum finding is basically consistent with the previously reported data in Chinese patients. The most common c.609G > A mutation may likely lead to early-onset cblC disease. In previous literature involving a large sample of Caucasian cblC cases, the mutation spectrum of MMACHC gene is almost completely different from that of the Chinese population. The most common mutations in the Caucasian population were c.271dupA, c.394C > T and c.331C > T, which account for 48.05% (542/1128), 13.65% (154/1128) and 7.36% (83/1128) of all the mutant alleles, respectively. The c.271dupA mutation and c.331C > T mutation were mainly associated with early-onset cblC in children less than 1 year old, whilst the c.394C > T mutation was mainly associated with late-onset cblC patients characterised by isolated acute nervous system abnormalities. We also analysed the cause behind the different mutation spectrum of MMACHC gene between the Chinese and Caucasian populations.     

Fine‐needle aspiration of alveolar soft part sarcoma: Histologic correlation and aberrant CD68 expression

Alveolar soft part sarcoma is a rare highly malignant neoplasm of the soft tissue and usually occurs in the lower extremities of children and young adults. We report two cases of alveolar soft part sarcoma: a 24‐year‐old Latino man with a 10‐ cm neck mass and a 56‐year‐old Latino woman with a recurring thigh mass. Fine‐needle aspiration and a core biopsy were performed on both, which was followed by tumor resection on the man. The smears displayed numerous loosely cohesive or single large cells with abundant granular cytoplasm, round nuclei, vesicular chromatin, and occasional prominent nucleoli. Periodic and Schiff (PAS)‐positive, diastase‐resistant rhomboid, or needle‐shaped crystals were present. Both tumors had diffuse and strong nuclear TFE3 expression and aberrant cytoplasmic CD68 expression. Fluorescence in situ hybridization analysis was performed in the first case, which detected a characteristic translocation t(X;17)(p11;q25). The diagnosis of alveolar soft part sarcoma was rendered in both cases. Herein, we present the cytology, histology, immunohistochemistry, and molecular findings and discuss the differential diagnosis.     

Who Is a Better Donor for Recipients of Allogeneic Hematopoietic Cell Transplantation: A Young HLA-Mismatched Haploidentical Relative or an Older Fully HLA-Matched Sibling or Unrelated Donor?

T cell replete HLA-mismatched haploidentical transplantation (HIDT) with post-transplant cyclophosphamide is increasingly becoming an acceptable treatment approach for patients lacking timely access to a suitably matched related donor transplant (MRDT) or matched unrelated donor transplant (MUDT). Multiple recent registry and single-center studies have shown comparable overall survival (OS) and disease-free survival (DFS) rates among HIDT, MRDT, and MUDT with a significantly lower risk of acute and chronic graft-versus-host disease (GVHD) among HIDT recipients. Candidates for allogeneic hematopoietic stem cell transplantation (HSCT) often have access to multiple donor sources, and a relevant question is whether outcomes can be improved with a younger HLA-mismatched haploidentical donor (≤35 years) rather than an older matched related donor (≥35 years) or matched unrelated donor (≥35 years). We analyzed 406 consecutive allogenic HSCT recipients, with a median age of 54 years (range, 19 to 77), after a MRDT with a donor age of ≥35 years (n = 222), MUDT with a donor age of ≥35 years (n = 91), and HIDT with a donor age of ≤35 years (n = 93). Median follow-up time for survivors was 51.5 months. Compared with MRDT and MUDT, HIDT recipients had a similar median age at time of HSCT, hematopoietic cell transplant comorbidity index, disease risk index distribution, and donor recipient sex matching. The survival estimates and relapse incidence at 3 years post-HSCT were OS (64% for MRDT, 54% for MUDT, and 62% for HIDT), DFS (55% for MRDT, 44% for MUDT, and 58% for HIDT), Transplant related mortality (TRM) (19% for MRDT, 16% for MUDT, and 18% for HIDT), and relapse (26% for MRDT, 37% for MUDT, and 24% for HIDT). HIDT recipients had better 3-year relapse rates compared with MUDT recipients (24% versus 37%, P= .048), with similar DFS and OS in a univariate analysis. MRDT recipients had a better relapse rate (26% versus 37%, P = .042) compared with MUDT recipients. Recipients of HIDT also had significantly lower rates of moderate to severe chronic GVHD compared with MRDT and MUDT recipients (P = .01). Multivariable analysis showed no effect of donor on OS, DFS, relapse, and TRM. Recipients of HIDT from a young donor ≤35 years had similar OS, lower rates of chronic GVHD, and better chronic GVHD-free, relapse-free survival compared with patients undergoing transplantation with an MRD or a MUD donor ≥35 years. This study suggests that given a situation where a choice between a young haploidentical relative and an older matched unrelated donor is to be made, one can achieve similar survival with a haploidentical donor and significantly lower rates of chronic GVHD.     

Fludarabine and Total-Body Irradiation Conditioning before Ablative Haploidentical Transplantation: Long-Term Safety and Efficacy

Although myeloablative conditioning (MAC) before haploidentical donor transplant (HIDT) with post-transplant cyclophosphamide is being increasingly used, the optimal preparative regimen remains unclear. In our initial trial, the feasibility of HIDT following a MAC preparative regimen using fludarabine and 12 Gy of total-body irradiation was demonstrated in 30 patients. We now present long-term outcome results, including an additional 52 patients, now with 47 months (16 to 96) median follow-up. Median patient age was 42 (19 to 61) years. The most common diagnoses were acute myelogenous leukemia (51%) and acute lymphoblastic leukemia (33%), and 39% had a high/very high disease risk index (DRI). Engraftment was universal with no cases of primary or secondary graft failure. Grade 3 to 4 acute graft-versus-host disease (GVHD) and moderate to severe chronic GVHD occurred in 17% and 23%, respectively. Nonrelapse mortality (NRM) was 7% at 1 year and 13% at 4 years. Estimated 4-year overall survival (OS), disease-free survival, and cumulative incidence of relapse (CIR) were 67%, 60%, and 27%, respectively. CIR was significantly higher in patients with high/very high- versus low/intermediate-risk DRI (38% versus 20%, P= .032), which led to inferior 4-year OS (50% versus 77%, P = .001). Median time to systemic immunosuppressive therapy (IST) discontinuation was 7.8 months, with 84% of patients off IST at 2 years post-transplant. Current GHVD-free, relapse-free survival (CGRFS) at 2, 3, and 4 years was 60%, 57%, and 60%, respectively. This approach to MAC HIDT results in universal engraftment; low rates of NRM, infection, and clinically significant GVHD; and relatively rapid IST discontinuation, resulting in high rates of CGRFS and survival.     

浅表食管癌侵袭深度及分化程度与区域淋巴结转移的临床分析

目的探讨浅表食管癌侵袭深度及分化程度与区域淋巴结转移的关系。方法本院2002年6月至2004年6月总共手术治疗食管癌923例,其中早期浅表食管癌68例,本文就对其术后侵袭深度及分化程度与区域淋巴结转移情况进行回顾性分析。结果本组无手术死亡,全组淋巴结转移率27%,其中高出黏膜型食管癌的淋巴结转移率为38%,侵袭越深,淋巴结转移率越高;分化程度越低淋巴结转移率越高。结论高度重视浅表型食管癌的根治性,对早期食管癌也应按肿瘤外科的原则行食管的次全切除术并常规清扫区域淋巴结。     

The mediating and moderating effects of resilience on the relationship between perceived stress and depression in heroin addicts

The purpose of this study was to examine the mediating and moderating roles of resilience on the relationship between perceived stress and depression among heroin addicts. A total of 138 heroin addicts completed the measures of perceived stress, resilience, and depression. Correlation analysis indicated that perceived stress was positively associated with depression. Resilience was negatively correlated with perceived stress and depression. Mediation analysis revealed that resilience partially mediated the relationship between perceived stress and depression. However, resilience did not moderate the influence of perceived stress on depression. These findings might provide a better understanding of the mental health among heroin addicts.