Single-cell mapping reveals several immune subsets associated with liver metastasis of pancreatic ductal adenocarcinoma.

BACKGROUND: Identifying a metastasis-correlated immune cell composition within the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) will help to develop promising and innovative therapeutic strategies. However, the dynamics of immune cell lineages in the TME of advanced PDAC remains elusive. METHODS: Twenty-six samples from 11 patients (including 11 primary tumor tissues, 10 blood, and 5 lymph nodes) with different stages were used to develop a multiscale immune profile. High-dimensional single-cell analysis with mass cytometry was performed to search for metastasis-correlated immune changes in the microenvironment. The findings were further validated by published single-cell RNA sequencing (scRNA-seq) data and multiplex fluorescent immunohistochemistry. FINDINGS: High-dimensional single-cell profiling revealed that the three immune-relevant sites formed a distinct immune atlas. Interestingly, the PDAC microenvironment with the potential for metastatic spread to the liver was characterized by a decreased proportion of CD103+PD-1+CD39+ T cells with cytotoxic and exhausted functional status and an increased proportion of CD73+ macrophages. Analysis of scRNA-seq data of PDAC further confirmed the identified subsets and revealed strong potential interactions via various ligand-receptor pairs between the identified T subsets and the macrophages. Moreover, stratified patients with different immune compositions correlated with clinical outcomes of PDAC. CONCLUSIONS: Our study uncovered metastasis-correlated immune changes, suggesting that ecosystem-based patient classification in PDAC will facilitate the identification of candidates likely to benefit from immunotherapy. FUNDING: This work was supported by the National Key Research and Development Program of China, the Shanghai International Science and Technology Collaboration Program, the Shanghai Sailing Program, and the Key Laboratory of diagnosis and treatment of severe hepato-pancreatic diseases of Zhejiang Province.

Theory-Guided Synthesis of Highly Luminescent Colloidal Cesium Tin Halide Perovskite Nanocrystals.

The synthesis of highly luminescent colloidal CsSnX3 (X = halogen) perovskite nanocrystals (NCs) remains a long-standing challenge due to the lack of a fundamental understanding of how to rationally suppress the formation of structural defects that significantly influence the radiative carrier recombination processes. Here, we develop a theory-guided, general synthetic concept for highly luminescent CsSnX3 NCs. Guided by density functional theory calculations and molecular dynamics simulations, we predict that, although there is an opposing trend in the chemical potential-dependent formation energies of various defects, highly luminescent CsSnI3 NCs with narrow emission could be obtained through decreasing the density of tin vacancies. We then develop a colloidal synthesis strategy that allows for rational fine-tuning of the reactant ratio in a wide range but still leads to the formation of CsSnI3 NCs. By judiciously adopting a tin-rich reaction condition, we obtain narrow-band-emissive CsSnI3 NCs with a record emission quantum yield of 18.4%, which is over 50 times larger than those previously reported. Systematic surface-state characterizations reveal that these NCs possess a Cs/I-lean surface and are capped with a low density of organic ligands, making them an excellent candidate for optoelectronic devices without any postsynthesis ligand management. We showcase the generalizability of our concept by further demonstrating the synthesis of highly luminescent CsSnI2.5Br0.5 and CsSnI2.25Br0.75 NCs. Our findings not only highlight the value of computation in guiding the synthesis of high-quality colloidal perovskite NCs but also could stimulate intense efforts on tin-based perovskite NCs and accelerate their potential applications in a range of high-performance optoelectronic devices.

[Treatment of Knee Osteoarthritis with Acupuncture plus Intra-articular Injection of Sodium Hyaluronate].

OBJECTIVE: To examine the clinical benefits of acupuncture combined with intra-articular injection of sodium hyaluronate for knee osteoarthritis (KOA) patients. METHODS: A total of 150 KOA patients were randomized into simple medication and acupuncture plus medication (combined treatment) groups (n＝75 in each). For all the patients, intra-articular injection of sodium hyaluronate (2 mL) was performed once a week for 5 weeks, and for patients of the combined treatment group, filiform needles were separately inserted into unilateral or bilateral Zusanli (ST 36), Liangqiu (ST 34), Yanglingquan (GB 34), Yinlingquan (SP 9), Xiyangguan (GB 33), Dubi (ST 35), Neixiyan (EX-LE 4) and Xuehai (SP 10) according to the focus, and manipulated with the uniform reinforcing and reducing technique, followed by retaining the needles for 30 min. The acupuncture treatment was given once every day or every other day, 5 weeks in total. The visual analog scale (VAS) was used to assess the pain severity of knee-joint, and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) employed to assess the 1) pain severity during various positions or movements (20 points), 2) severity of joint stiffness (8 points), and 3) difficulty in performing daily functional activities (68 points). The therapeutic effect was evaluated according to the decreased level of WOMAC subscale scores and improvement of daily activities. RESULTS: After the treatment, the VAS scores of both medication and combined treatment groups were decreased significantly in comparison with their own pre-treatment in each group (P<0.05), and that of the combined treatment group was significantly lower than that of the medication group (P<0.05). WOMAC and daily activity fin-dings showed that of the two 75 KOA patients in the medication and combined treatment groups, 16 (21.33%) and 32 (42.67%) experienced marked improvement, 46 (61.33%) and 38 (50.67%) were improved, and 13 (17.33%) and 5 (6.67%) ineffective, with the total effective rates being 82.67% and 93.33%, respectively. The therapeutic effect of the combined treatment group was apparently superior to that of the simple medication group (P<0.05). CONCLUSION: Acupuncture combined with intra-articular injection of sodium hyaluronate is effective in improving KOA patients' pain severity and other symptoms as well as functional activities.

Echocardiography detection of fetal ventricular aneurysm: A report of three cases.

From March 2007 to September 2009, we have screened with echocardiography a total of 6,502 pregnant women for fetal heart disease. We found three cases of fetal ventricular aneurysm. The relatively large size of the aneurysm in these three cases was clearly visible under standard four-chamber view. Two were right ventricular aneurysms arisen from the ventricular free wall, and both showed characteristics of true aneurysm with a thin wall and a large communication with the ventricular chamber. Color Doppler showed passive movement of aneurysm during right ventricle contraction. The third case was a large left ventricular aneurysm outpouching from a small opening of the left ventricular wall close to the apical region. © 2014 Wiley Periodicals, Inc. J Clin Ultrasound 43:257-261, 2015.

[Essential oil from Artemisia lavandulaefolia induces apoptosis and necrosis of HeLa cells].

OBJECTIVE: To investigate the effects of Artemisia lavandulaefolia essential oil on apoptosis and necrosis of HeLa cells. METHODS: Cell viability was assayed using MTT method. The morphological and structure alterations in HeLa cells were observed by microscopy. Furthermore, cell apoptosis was measured by DNA Ladder and flow cytometry. DNA damage was measured by comet assay, and the protein expression was examined by Western blot analysis. RESULTS: MTT assay displayed essential oil from Artemisia lavandulaefolia could inhibit the proliferation of HeLa cells in a dose-dependent manner. After treated with essential oil of Artemisia lavadulaefolia for 24 h, HeLa cells in 100 and 200 microg/mL experiment groups exhibited the typical morphology changes of undergoing apoptosis, such as cell shrinkage and nucleus chromatin condensed. However, the cells in the 400 microg/mL group showed the necrotic morphology changes including cytomembrane rupture and cytoplasm spillover. In addition, DNA Ladder could be demonstrated by DNA electrophoresis in each experiment group. Apoptosis peak was also evident in flow cytometry in each experiment group. After treating the HeLa cells with essential oil of Artemisia lavadulaefolia for 6 h, comet tail was detected by comet assay. Moreover, western blotting analysis showed that caspase-3 was activated and the cleavage of PARP was inactivated. CONCLUSION: Essential oil from Artemisia lavadulaefolia can inhibit the proliferation of HeLa cells in vitro. Low concentration of essential oil from Artemisia lavadulaefolia can induce apoptosis, whereas high concentration of the compounds result in necrosis of HeLa cells. And,the mechanism may be related to the caspase-3-mediated-PARP apoptotic signal pathway.