Primary leptomeningeal melanocytic neoplasms: A clinicopathologic, immunohistochemical, and molecular study of 12 cases.

This study investigated the clinicopathological, immunohistochemical, and molecular features of primary leptomeningeal melanocytic neoplasms (LMNs). Twelve LMN cases were retrospectively reviewed. We performed Fluorescence in-situ hybridization (including a 4-probe FISH assay with CDKN2A and MYC assay) and Next-Generation sequencing analyses on available cases. Histologically, 2 tumours were classified as melanocytomas (MC), 2 as intermediate-grade melanocytomas (IMC), and 8 as leptomeningeal melanomas (LMM). Two rare cases of LMM were associated with large plaque-like blue nevus. One MC case was associated with Ota. Ten cases (83.3%) showed melanocytic cells with benign features diffusely proliferating within the meninges. The Ki-67 in three categories differed (MC 0-1%, IMC 0-3%, LMM 3-10%). 57.1% of LMM cases (4/7) were positive for FISH. Nine of 10 tumours harboured activating hotspot mutations in GNAQ, GNA11, or PLCB4. Additional mutations of EIF1AX, SF3B1, or BAP1 were found in 40%, 30%, and 10% of tumours, respectively. During the follow-up (median = 43 months), 5 LMM patients experienced recurrence and/or metastasis, 3 of them died of the disease and the other 2 are alive with the tumour. Our study is by far the first cohort of LMN cases tested by FISH. In addition to morphological indicators including necrosis and mitotic figures, using a combination of Ki-67 and FISH helps to differentiate between IMC and LMM, especially in LMM cases with less pleomorphic features. SF3B1 mutation is first described in 2 cases of plaque-type blue nevus associated with LMM. Patients with SF3B1 mutation might be related to poor prognosis in LMN.

3D printed elastic hydrogel conduits with 7,8-dihydroxyflavone release for peripheral nerve repair.

Nerve guide conduit is a promising treatment for long gap peripheral nerve injuries, yet its efficacy is limited. Drug-releasable scaffolds may provide reliable platforms to build a regenerative microenvironment for nerve recovery. In this study, an elastic hydrogel conduit encapsulating with prodrug nanoassemblies is fabricated by a continuous 3D printing technique for promoting nerve regeneration. The bioactive hydrogel is comprised of gelatin methacryloyl (GelMA) and silk fibroin glycidyl methacrylate (SF-MA), exhibiting positive effects on adhesion, proliferation, and migration of Schwann cells. Meanwhile, 7,8-dihydroxyflavone (7,8-DHF) prodrug nanoassemblies with high drug-loading capacities are developed through self-assembly of the lipophilic prodrug and loaded into the GelMA/SF-MA hydrogel. The drug loading conduit could sustainedly release 7,8-DHF to facilitate neurite elongation. A 12 â€‹mm nerve defect model is established for therapeutic efficiency evaluation by implanting the conduit through surgical suturing with rat sciatic nerve. The electrophysiological, morphological, and histological assessments indicate that this conduit can promote axon regeneration, remyelination, and function recovery by providing a favorable microenvironment. These findings implicate that the GelMA/SF-MA conduit with 7,8-DHF release has potentials in the treatment of long-gap peripheral nerve injury.

3D printing of microneedle arrays for hair regeneration in a controllable region.

Hair loss is a common skin disease that causes intense emotional suffering. Hair regeneration in a personalized area is highly desirable for patients with different balding conditions. However, the existing pharmaceutical treatments have difficulty precisely regenerating hair in a desired area. Here, we show a method to precisely control the hair regeneration using customized microneedle arrays (MNAs). The MNA with a customized shape is fast fabricated by a static optical projection lithography process in seconds, which is a 3D printing technology developed by our group. In the mouse model, MNA treatment could induce hair regrowth in a defined area corresponding to the customized shape of MNA. And the regenerated hair promoted by MNAs had improved quality. Cellular and molecular analysis indicated that MNA treatment could recruit macrophages in situ and then initiate the proliferation of hair follicle stem cells, thereby improving hair regeneration. Meanwhile, the activation of the Wnt/ß-catenin signaling pathway was observed in hair follicles. The expressions of Hgf, Igf 1 and Tnf-α were also upregulated in the treated skin, which may also be beneficial for the MNA-induced hair regeneration. This study provides a strategy to precisely control hair regeneration using customized microneedle arrays by recruiting macrophages in situ, which holds the promise for the personalized treatment of hair loss.

Desmoplastic Small Round Cell Tumor of the Head and Neck: A Clinicopathological, Immunohistochemical and Molecular Analysis of Three Cases with Literature Review.

Desmoplastic small round cell tumor (DSRCT) is a rare aggressive malignancy typically originating from the abdominal or pelvic cavity. DSRCT presenting as a primary head and neck tumor has rarely been described in the literature. We present three cases of DSRCT arising in the head and neck to further characterize its clinicopathological features. All three patients were male and aged 36, 30 and 17 years. The involved sites included the orbit (1 case) and submandibular gland (2 cases). The tumors ranged in size from 2.4 to 3.5 cm (mean, 2.1 cm). Histologically, all tumors showed irregular-shaped, variable-sized nests of small round cells deposited in an abundant desmoplastic stroma. Tumor cells contained scant amounts of eosinophilic cytoplasm and small hyperchromatic nuclei with inconspicuous nucleoli. Immunohistochemically, the tumors were positive for keratin (AE1/AE3) (3/3), desmin (3/3), vimentin (2/2), NSE (1/1) and EMA (1/1). Fluorescence in situ hybridization (FISH) analysis demonstrated the presence of EWSR1 and WT1 rearrangements in all three cases. All patients received surgery and adjuvant chemotherapy and/or radiotherapy. There was no evidence of recurrence and metastasis in two patients, and the third suffered lung metastasis. DSRCT arising in the head and neck represents an extremely rare condition. It is easily mistaken as poorly differentiated carcinoma due to similar morphology and expression of epithelial markers. Immunohistochemistry assay in conjunction with molecular detection of EWSR1::WT1 fusion will be helpful for arriving at an accurate diagnosis to avoid misdiagnosis and inappropriate treatment.

3D-printed microneedle arrays for drug delivery.

Microneedle arrays provide an efficient tool for transdermal drug delivery in a minimally invasive and painless manner, showing great potential applications in medicine. However, it remains challenging to fabricate the desired microneedle arrays, because of their micron-scale size and fine structure. Novel manufacturing technologies are very wanted for the development of microneedle arrays, which would solidly advance the clinical translation of microneedle arrays. 3D printing technology is a powerful manufacturing technology with superiority in fabricating personalized and complex structures. Currently, 3D printing technology has been employed to fabricate microneedle arrays, which could push more microneedle arrays into clinic and inspire the development of future microneedle arrays. This work reviews the art of 3D printing microneedle arrays, the benefits of fabricating microneedle arrays with 3D printing, and the considerations for clinical translation of 3D-printed microneedle arrays. This work provides an overview of the current 3D-printed microneedle arrays in drug delivery.

Fast Customization of Hollow Microneedle Patches for Insulin Delivery.

Hollow microneedle patches (HMNPs) have great promise for efficient and precise transdermal drug delivery in a painless manner. Currently, the clinical application of HMNPs is restricted by its complex manufacturing processes. Here, we use a new three-dimensional (3D) printing technology, static optical projection lithography (SOPL), for the fast fabrication of HMNPs. In this technology, a light beam is modulated into a customized pattern by a digital micromirror device (DMD) and projected to induce the spatial polymerization of monomer solutions which is controlled by the distribution of the light intensity in the monomer solutions. After an annulus picture is inputted into the DMD via the computer, the microneedles with hollow-cone structure can be precisely printed in seconds. By designing the printing pictures, the personalized HMNPs can be fast customized, which can afford the scale-up preparation of personalized HMNPs. Meanwhile, the obtained hollow microneedles (HMNs) have smooth surface without layer-by-layer structure in the commonly 3D-printed products. After being equipped with a micro-syringe, the HMNPs can efficiently deliver insulin into the skin by injection, resulting in effective control of the blood glucose level in diabetic mice. This work demonstrates a SOPL-based 3D printing technology for fast customization of HMNPs with promising medical applications.

Pneumatosis cystoides intestinalis accompanied by schistosomiasis: a case report.

Pneumatosis cystoides intestinalis (PCI) is a rare disease that most frequently occurs in the large and small intestine and has no obvious clinical symptoms. The main pathological feature is the presence of air-filled cysts in the intestinal submucosa, intermuscular wall, and subserous membrane. Conservative treatment is the first choice when no serious complications are present, whereas timely surgical treatment is needed for serious and life-threatening complications. This report presents the clinical and pathological analysis of PCI in a man in his early 90s. The patient was hospitalized because of acute abdomen and diagnosed with perforation of the sigmoid colon due to PCI with schistosomiasis after emergency surgery. Emergency partial sigmoid colon resection and permanent colostomy were performed under general anesthesia. Preoperative diagnosis of PCI is difficult because of the nonspecific clinical manifestations and endoscopic findings, and missed diagnosis and misdiagnosis easily occur. Pure PCI has no specific symptoms and does not require special treatment, and there is a lack of special treatment methods in clinical practice. However, when PCI is combined with other intestinal diseases such as schistosomiasis enteropathy, intestinal perforation is likely to occur, leading to severe acute abdomen with the need for prompt surgical treatment.

Fast Customization of Microneedle Arrays by Static Optical Projection Lithography.

Customized microneedle arrays (CMNAs) hold great promise for precise transdermal delivery in a minimally invasive manner. Currently, the fast customization of microneedle arrays remains a great challenge. Here, we show a static optical projection lithography (SOPL) technology for fast 3D printing CMNAs. In this technology, the digital light is statically projected to induce the spatial polymerization of monomer solutions, and therefore microneedle formation can be precisely controlled by the intensity distribution of the projected light. The obtained CMNAs do not have the stair-like surface and layer-by-layer structure that are associated with the common 3D-printing technologies. This method enables fast fabrication of CMNAs with designed shape, size, and distribution in seconds without mechanical motion system. Up-conversion nanoparticles (UCNPs) were delivered into skin by the CMNAs, to form a personalized dot matrix for in vivo information storage. Under the irradiation of near-infrared (NIR) light, the UCNPs in skin displayed a visible dot matrix, presenting information encoded in the structure of CMNAs. This work demonstrates a SOPL technology for rapidly customizing high-quality microneedle arrays and a CMNA-mediated in vivo information storage strategy.

Effect of reflectance confocal microscopy compared to dermoscopy in the diagnostic accuracy of lentigo maligna: A meta-analysis.

INTRODUCTION: Many concerns were raised about the sensitivity and specificity outcome of reflectance confocal microscopy compared to dermoscopy for the diagnosis of lentigo maligna. However, the reported relationships between their sensitivity and specificity were variable. Our meta-analysis was performed to clarify this relationship. METHODS: A systematic literature search up to July 2020 was performed and six included studies had 479 subjects at the baseline with 294 undergoing lentigo maligna diagnoses. They were reporting relationships between sensitivity and specificity outcome of reflectance confocal microscopy compared to dermoscopy for the diagnosis of lentigo maligna. Mean difference (MD) with 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of the sensitivity and specificity of reflectance confocal microscopy compared to dermoscopy for the diagnosis of lentigo maligna using the continuous method with a random or fixed-effect model. RESULTS: Reflectance confocal microscopy was significantly related to higher specificity (MD, 19.10; 95% CI, 0.93-37.28, P = .04) compared to dermoscopy in lentigo maligna diagnosis. However, reflectance confocal microscopy was only relatively but not significantly related to higher sensitivity (MD, 14.56; 95% CI, 0.29-28.83, P = .05) compared to dermoscopy in lentigo maligna diagnosis. CONCLUSIONS: Based on this meta-analysis, the reflectance confocal microscopy compared to dermoscopy in lentigo maligna diagnosis had a significantly higher specificity and relatively higher sensitivity. This relationship forces us to recommend reflectance confocal microscopy in lentigo maligna diagnosis for better outcomes and to avoid any possible false-negative results. Further studies are required.

Expression of tumor necrosis factor alpha-induced protein 3 mRNA in peripheral blood mononuclear cells negatively correlates with disease severity in psoriasis vulgaris.

Psoriasis vulgaris is considered a chronic inflammatory disease, but its immunopathogenesis has not been well understood. The tumor necrosis factor alpha-induced protein 3 (TNFAIP3) gene functions in negative-feedback regulation of inflammation, and its single nucleotide polymorphism is associated with psoriasis. However, the relationship between the expression level of the TNFAIP3 gene in immune cells and psoriasis is not known so far. In the present study, TNFAIP3 mRNA expression levels in peripheral blood mononuclear cells from 44 patients with psoriasis vulgaris and 30 healthy controls were determined using real-time reverse transcription-PCR analysis. We found that expression of TNFAIP3 mRNA in all patients negatively correlated with the psoriatic area and severity index (PASI) (r = -0.5126; P = 0.0004) as well as with the percentage of body surface area affected by psoriasis (r = -0.5013; P = 0.0005). Patients were divided into mild and severe groups based on the mean PASI score. Expression of TNFAIP3 mRNA in the mild group was higher than that in the severe group (P = 0.0064). Moreover, compared with that in healthy controls, the expression of TNFAIP3 mRNA in the mild group was significantly upregulated (P = 0.0004), but the expression of TNFAIP3 mRNA in the severe group was not. These results suggest that the expression level of TNFAIP3 plays an important role in the pathology of psoriasis vulgaris and that the loss of upregulation of TNFAIP3 expression may contribute to the severity of psoriasis vulgaris.

A two-dimensional undulating Ag(I) coordination polymer constructed of Ag-C and Ag-O bonds: poly[[[µ3-(5,6-η):κO(2):κO(2)-(±)-(1S,2S,3R,4R)-3-carboxy-7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylato]silver(I)] monohydrate].

The title coordination polymer, {[Ag(C(8)H(7)O(5))]·H(2)O}(n), is built from Ag(+) cations and singly protonated dehydronorcantharidin (SP-DNC) anions, with a distorted trigonal-planar geometry at the metal centre. The coordination number of Ag(I) is three (with one Ag-π bond and two Ag-O bonds, one from each of three different SP-DNC ligands), if only formal Ag-ligand bonds are considered, but can be regarded as five if longer weak Ag···O interactions are also included. The two-dimensional corrugated-sheet coordination polymer forms a non-interpenetrating framework with (4.8(2)) topology. Disordered water molecules are sandwiched between the sheets.

[Research advance on clinical blood transfusion and tumor therapy].

Clinical blood transfusion is one of the most important supportive therapy for patients with tumor. The blood transfusion has dual effects for patients with tumor. First, blood transfusion can rectify anemia and improve oxygen saturation, accelerate oxidation and necrosis for tumor cells; the second, blood transfusion can induce immunosuppression, tumor recurrence and postoperative infection for tumor patients. Filtering white blood cells (WBC) before blood transfusion can decrease the incidence of the adverse reactions. The rational perioperative autotransfusion for patients with tumors is focus to which the world medical sciences pay close attention. In this article, the support effect of blood transfusion for treatment of tumor patients, blood transfusion and immunosuppression, blood transfusion and postoperative infection and relapse of tumor patients, depleted leukocyte blood transfusion and autologous transfusion of tumor patients are reviewed.