锥形束CT在鼻泪管阻塞性疾病辅助诊断中的应用价值

目的 探讨锥形束CT （CBCT）在鼻泪管阻塞性疾病辅助诊断中的应用价值。方法 选取2018年1月至2020年8月在中国人民解放军总医院眼科门诊就诊的鼻泪管阻塞性疾病患者104例，按随机数字表法分为观察组及对照组，各52例，观察组患者采用CBCT检查鼻泪管，对照组采用CT泪道造影检查鼻泪管。观察并比较两组患者鼻泪管的影像解剖形态、解剖参数（骨性鼻泪管长度、中段管径最小横径、管径最小面积）及剂量长度乘积。结果 两种成像方法均可清楚观察患者骨性鼻泪管的解剖形态，清晰显示骨性鼻泪管的阻塞情况及周围组织结构。两组患者鼻泪管斜冠状位的长度、中段最窄处的横径及横截面积比较，差异均无统计学意义（P<0.05）。观察组患者剂量长度乘积为50.35 mGy.cm，是对照组剂量长度乘积的1/6左右。结论 与CT泪道造影比较，CBCT成像可以精准显示鼻泪管阻塞性疾病患者鼻泪管引流状态，明确阻塞部位和程度，且具有辐射剂量低、空间分辨率高等优点。     

“耳脑脏腑相关”理论构建＊

通过系统整理中医传统理论中耳与脑、脏腑与脑、耳与脏腑之间的联系，结合体表刺激耳迷走神经-孤束核-默认网络脑效应机制研究，将传统针灸与现代医学相融合，提出“耳脑脏腑”相关理论。刺激耳甲的耳穴心不仅可以直接调节心神，通过耳脑相关机制调理脑与脑神，还可以配合或间接刺激耳甲区的五脏，调理五脏之神（心神、肝魂、肺魄、脾意和肾志），从而实现神脑并调和体用兼治之功，对于脑失常、神失常、五脏神失常类的疾病，理论上来说，具有较好的临床疗效。“耳脑脏腑相关”理论的提出，对于揭示采用耳穴心治疗脑系疾病和相关脏腑病提供了理论支持，对于加强中医原创理论创新提供典型范例，实现了继承与创新的结合，对于现代拓展脑病、脑科学和相关脏腑病研究提供了新方向和新思路。     

Adrenal tumors of different types with or without tumor thrombus invading the inferior vena cava: An evaluation of 33 cases

Background and objectivesAdrenal tumors with/out tumor thrombus (TT) in the inferior vena cava (IVC) pose a challenge to the surgeon due to the potential of massive hemorrhage and tumor thromboembolism. We report our experience in managing different types of adrenal tumors.MethodsFrom 11/1996–5/2015, 33 patients underwent resection of adrenal tumors with/without TT/IVC in 8 and 25 patients, respectively. Transplant-based (TB) techniques were utilized to resect the tumors. Intra-operative as estimated blood loss (EBL) and cardiopulmonary bypass (CPB) use; post-operative as length of hospital stay (LOS); and actuarial survival outcomes were recorded.ResultsMedian EBL was 200 cc (10-8,000), tumor size was 9.0 cm (4–25), and LOS was 7days (5–60). Adrenocortical carcinoma (ACC,11/33) was the commonest type. Three ACC/level IV TT/IVC underwent CPB to extract TT from the right atrium(n = 1), right atrium and right ventricle(n = 1), and right atrium and right pulmonary artery(n = 1), respectively. A complete resection of the adrenal tumors was achieved in all patients, and no deaths were observed in the immediate postoperative period. With a median follow-up of 60 (range: 18–120) months, 4/11 ACC patients have died of their disease. Actuarial survival for ACC patients at 60 months was 57.1 ± 16.4%.ConclusionsAn aggressive surgical approach is the only hope for curing large adrenal tumors with/without TT/IVC. TB techniques provide excellent exposure to the retroperitoneal space and safe removal of large adrenal masses.     

Breast cancer detection by dedicated breast positron emission tomography according to the World Health Organization classification of breast tumors

ObjectiveConsidering the difficulty in detecting primary breast cancers using whole-body positron emission tomography (WBPET) owing to its limited spatial resolution, we aimed to evaluate the detectability of breast cancer by ring-type dedicated breast PET (DbPET) on the World Health Organization (WHO) histological classification in comparison with WBPET.MethodsA total of 938 patients with breast cancer underwent WBPET and ring-type DbPET, and 1021 lesions were histologically assessed based on the WHO classification of tumors of the breast. The findings of WBPET and DbPET were retrospectively evaluated and compared.ResultsThe size-related sensitivity of DbPET was superior to that of WBPET for subcentimetric tumors (81.9% vs. 52.4%, P < 0.001). The histological distribution was as follows: 11 lobular carcinoma in situ, 158 ductal carcinoma in situ, 738 infiltrating duct carcinoma not otherwise specified (NOS), 12 lobular carcinoma NOS, 40 mucinous adenocarcinoma, 13 tubular carcinoma, 36 invasive breast carcinoma others, and 13 papillary neoplasms. WBPET had low sensitivity for lobular carcinoma in situ, ductal carcinoma in situ, lobular carcinoma NOS, mucinous adenocarcinoma, and tubular carcinoma. DbPET showed improved sensitivity for all the above except lobular and tubular carcinoma. The maximum standardized uptake values (SUVmax) of DbPET were significantly higher than those of WBPET for histological types, excluding lobular carcinoma in situ. The SUVmax of papillary neoplasms was high regardless of low-grade histology and Ki-67 labeling index.ConclusionsDBPET was found to have high sensitivity and SUVmax values for all histologic types that showed low sensitivity of detection on WBPET, except lobular carcinoma in situ.     

Interactions with PDZ proteins diversify voltage‐gated calcium channel signaling

Voltage‐gated Ca²⁺ (Ca_V) channels are crucial for neuronal excitability and synaptic transmission upon depolarization. Their properties in vivo are modulated by their interaction with a variety of scaffolding proteins. Such interactions can influence the function and localization of Ca_V channels, as well as their coupling to intracellular second messengers and regulatory pathways, thus amplifying their signaling potential. Among these scaffolding proteins, a subset of PDZ (postsynaptic density‐95, Drosophila discs‐large, and zona occludens)‐domain containing proteins play diverse roles in modulating Ca_V channel properties. At the presynaptic terminal, PDZ proteins enrich Ca_V channels in the active zone, enabling neurotransmitter release by maintaining a tight and vital link between channels and vesicles. In the postsynaptic density, these interactions are essential in regulating dendritic spine morphology and postsynaptic signaling cascades. In this review, we highlight the studies that demonstrate dynamic regulations of neuronal Ca_V channels by PDZ proteins. We discuss the role of PDZ proteins in controlling channel activity, regulating channel cell surface density, and influencing channel‐mediated downstream signaling events. We highlight the importance of PDZ protein regulations of Ca_V channels and evaluate the link between this regulatory effect and human disease.     

Downregulation of APRIN expression increases cancer cell proliferation via an interleukin-6/STAT3/cyclin D axis

APRIN is a putative tumor suppressor whose expression is low in a variety of cancer cells. While decreased expression of APRIN leads to increased cell proliferation, unfavorable diagnosis or metastases in various cancer types, there is limited knowledge on the cellular mechanism of APRIN in cellular responses. The effect of APRIN depletion on cancer cell proliferation was examined in the present study, and the IL-6/STAT3/cyclin D axis was identified as a novel regulatory mechanism. Stable depletion of APRIN in cancer cells resulted in increased cell proliferation. Cytokine array analysis of the cells revealed that downregulation of APRIN induced secretion of interleukin-6 (IL-6) with corresponding activation of STAT3, a downstream intracellular mediator. Levels of cyclin D1 were increased in cells with APRIN depletion and cyclin D1 expression was associated with increased STAT3 binding on cyclin D1 promoter sequence; assessed by chromatin immunoprecipitation assay. The addition of an IL-6 neutralizing antibody P620 to the cell culture attenuated STAT3 activation and cyclin D1 expression in APRIN-depleted cells with corresponding decrease in cell proliferation. These experiments suggest that APRIN regulates cancer cell proliferation via an IL-6/STAT3/cyclin D axis and that targeting this axis in APRIN-associated cancer might provide a novel therapeutic approach.     

Hydroxyurea-induced genital ulcers and erosions: Two case reports

Hydroxyurea is a chemotherapeutic agent used for myeloproliferative disorders and sickle cell anemia that is well known to cause painful mucocutaneous ulcers, typically involving the legs or mouth. However, genital ulcerations due to hydroxyurea therapy are a rare, and likely underrecognized, adverse effect with only a few cases reported in the literature to date. Ulcers of the lower legs caused by hydroxyurea are associated with a diagnostic delay, and this is likely exacerbated in cases of genital ulceration due to a lack of awareness. Herein we present two cases of painful genital ulceration in patients on hydroxyurea therapy. In the first Case, an 87 year-old male with polycythemia vera developed an ulcer on the scrotum, which was assessed initially through virtual visits during the COVID-19 pandemic, and was refractory to topical and oral antibiotic treatments. The second case was a 79 year-old male with essential thrombocythemia and a history of persistent leg ulcers who developed erosions of the glans penis. Both patients experienced complete resolution within weeks of discontinuing hydroxyurea therapy. In conclusion, genital ulcers and erosions induced by hydroxyrea may be underrecognized in clinical practice, but if identified, withdrawal of hydroxyurea leads to quick resolution of these lesions and the associated pain.     

A case of a primary myelofibrosis with progression and related literature review of progression phase genetics

Philadelphia (BCR-ABL)-negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). MPN can transform into an accelerated or a blast phase, which is associated with poor response to standard therapy and low overall median survival. We present an interesting case of a patient with a history of PMF and progression and summarize the current studies on genetic features of myeloproliferative neoplasms in blast phase (MPN-BP) with an emphasis on PMF. Although MPN-BP show ≥20% blasts in peripheral blood or bone marrow, it is not considered as acute myeloid leukemia (AML) according to the WHO classification. While MPNs-BP typically lack genetic mutations seen in de novo AML, they commonly harbor IDH1/2, SRSF2, ASXL1, and TP53 mutations, similar to the genetic profiles of acute myeloid leukemia with myelodysplasia-related changes (AML-MRC).     

Understanding the genetic contribution of the human leukocyte antigen system to common major psychiatric disorders in a world pandemic context

The human leukocyte antigen (HLA) is a complex genetic system that encodes proteins which predominantly regulate immune/inflammatory processes. It can be involved in a variety of immuno-inflammatory disorders ranging from infections to autoimmunity and cancers. The HLA system is also suggested to be involved in neurodevelopment and neuroplasticity, especially through microglia regulation and synaptic pruning. Consequently, this highly polymorphic gene region has recently emerged as a major player in the etiology of several major psychiatric disorders, such as schizophrenia, autism spectrum disorder and bipolar disorder and with less evidence for major depressive disorders and attention deficit hyperactivity disorder. We thus review here the role of HLA genes in particular subgroups of psychiatric disorders and foresee their potential implication in future research. In particular, given the prominent role that the HLA system plays in the regulation of viral infection, this review is particularly timely in the context of the Covid-19 pandemic.