[Cerebrospinal fluid TP53 gene mutation in patients with lung cancer associated meningitis and its clinical implications].

Objective: To observe the role of cerebrospinal fluid (CSF) TP53 gene mutation in lung cancer associated meningitis. Methods: A retrospective analysis was performed on 35 patients diagnosed with lung cancer associated meningitis at the Second Hospital of Hebei Medical University from December 2015 to December 2018.All patients underwent the next-generation sequencing of CSF, and TP53 gene was found to be mutant or wild type, including 23 patients with TP53 mutant type and 12 patients with TP53 wild type. The clinical characteristics, CSF leukocyte, protein, glucose, chloride, Karnofsky performance (KPS) and overall survival were observed. Results: Headache, nausea and vomiting were the main clinical manifestations in both groups.There were no significant differences in CSF pressure, leukocyte, biochemical indicators and KPS between the two groups. The average time from diagnosis of lung cancer to diagnosis of lung cancer associated meningitis in the TP53 mutant group was significantly shorter than that in the TP53 wild type group (5.79 months vs 25.5 months).The median survival time of patients in the TP53 mutant group from lung cancer diagnosis to the observation endpoint was 19.77 months, while it was 88.73 months in the TP53 wild type group, and the difference was statistically significant (P=0.043). Conclusions: Mutation in the tumor suppressor gene TP53 can be detected in the CSF of patients with lung cancer associated meningitis. Patients with such mutation have earlier meningeal metastasis and shorter median survival time.

[Pollution characteristics and risk assessment of carcinogenicity or non-carcinogenicityonheavy metalsin Particulate Matter 2.5 in Shenzhen].

Objective: To assess the pollution characteristics and risk assessment of carcinogenicity or non-carcinogenicity on heavy metals in PM(2.5) in Shenzhen. Methods: PM(2.5) samples were collected monthly from the year of 2014 to 2015, and analyzed by seasons. 12 heavy metal elements (Pb, Hg, Mn, Sb, Al, As, Be, Cd, Cr, Ni, Se, Tl) in PM(2.5) were detected by ICP-MS spectrometry. Health risk assessment was conducted using the recommended United States Environmental Protection Agency (USA EPA) model. Results: The median of PM(2.5) concentration was 45.10 µg/m(3) in Longgang district of Shenzhen. The non-carcinogenecity risks of the metals in PM(2.5) existed in spring, autumn and winter (HQ>1). Three metal elements including As, Mn and Cd have higher HQ levels. The carcinogenecity risk levels in four seasons were winter, autumn, spring and summer, respectively. The carcinogenecity risks in four seasons were between 10(-6) to 10(-4). As, Cr and Cd have higher carcinogenicityrisks. Conclusion: The heavy metals in PM(2.5) have both carcinogenecity risk and non-carcinogenecity risk to residents in Longgang district of Shenzhen, the occupational health management must be continuously strengthened, the further research and the measures for prevention and control should be considered.

[Clinical effect of nano-fat mixed granule fat transplantation in the treatment of cicatricial facial depression and atrophy and the related experimental mechanism].

Objective: To study the clinical effect of nano-fat mixed granule fat transplantation in the treatment of cicatricial facial depression and atrophy, and to explore the related experimental mechanism. Methods: (1) From January 2012 to April 2018, 105 patients conforming to the inclusion criteria, with cicatricial facial depression and atrophy deformity who needed facial fat transplantation, were admitted to our unit. Their medical records were analyzed retrospectively. According to the patients' wishes, 54 patients (12 males and 42 females) aged 10-59 years received traditional transplantation of pure autologous granule fat collected from abdomen/thigh and were included in simple transplantation group, while the other 51 patients (14 males and 37 females) aged 7-63 years received transplantation of autologous nano-fat mixed granule fat collected from abdomen/thigh and were included in mixed transplantation group. The treatment satisfaction of patients 3 and 6 months after operation was assessed by the facial fullness, symmetry, scar, and complications using self-made scales and photo data before and after operation. Six months after operation, the patients were assessed whether they needed to undergo a second operation, and the rate of second operation was calculated. During the second operation, the fat of patients transplanted in the first operation was collected, and the morphology of adipocytes and microangiogenesis was observed under a scanning electron microscope. (2) Adipose-derived stem cells (ADSCs) were isolated and cultured from abdominal fat of a 4-week-old male Sprague-Dawley (SD) rat. The 5th passage of cells were selected to observe cell morphology after cultured for 14 days, observe expression of vimentin and cytokeratin-18 by immunofluorescence method, identify osteogenic and adipogenic differentiation, and detect rates of CD29 and CD44 positive cells by flow cytometer (n=3). Eighteen 4-week-old male SD rats were divided into ADSCs transplantation group, simple scar group, and blank control group according to the random number table, with 6 rats in each group. Rats in ADSCs transplantation group and simple scar group were subcutaneously injected with 1 mL bleomycin which was dissolved in phosphate buffered saline (PBS) with a mass concentration of 1 mg/mL at the back to establish scar models. After 3 hours, rats in ADSCs transplantation group were injected with 1×10(6) ADSCs suspended in 0.1 mL PBS at the same injection site, while rats in simple scar group were injected with 0.1 mL PBS. Rats in blank control group were injected with the same doses of PBS in the same place at the same two time points mentioned above. After continuous injection for 28 days in each group, the full-thickness skin tissue of the injected area of all rats was collected to observe the collagen fibers by Masson staining and expressions of α-smooth muscle actin (α-SMA) and transforming growth factor ß(1) (TGF-ß(1)) by immunohistochemistry, and the positive cells were counted. Data were processed with Mann-Whitney U test, χ(2) test, one-way analysis of variance, and least significant difference test. Results: (1) Compared with the preoperative condition, the facial fullness and symmetry of patients in simple transplantation group were better in 3 months after operation, with scar color closer to the surrounding skin, and the filling volume of patients in this group decreased in 6 months after operation as compared with that in 3 months after operation. In mixed transplantation group, the facial fullness and symmetry of patients were better in 3 and 6 months after operation as compared with the preoperative condition, with scar color and texture closer to the surrounding skin, and the filling volume in 6 months after operation was not obviously reduced as compared with that in 3 months after operation. Fat liquefaction and subcutaneous nodule formation occurred respectively in 1 patient in simple transplantation group within 3 months after operation. The treatment satisfaction of patients in mixed transplantation group was significantly higher than that in simple transplantation group in 3 and 6 months after operation (Z=-2.566, -3.084, P<0.05 or P<0.01). Six months after operation, the second operation rate of patients in mixed transplantation group was 7.84% (4/51), which was significantly lower than 22.22% (12/54) in simple transplantation group (χ(2)=4.199, P<0.05). At the second operation, compared with those of simple transplantation group, the cells of fat transplanted in the first operation of patients in mixed transplantation group were more plump, without collapse or dryness, and the cells were closely arranged, with smaller gap; the tubular and the cord-like microvascular structure on the cell surface were more abundant, and the cell gap was full of network-like microvascular structure that grew into the adipose tissue. (2) The fifth passage of cells isolated and cultured from rat fat grew adherently to the wall, with long fusiform or spindle shape, showing shoal-of-fish-like growth. Vimentin and cytokeratin-18 were highly expressed in the cells. Cells showed osteogenic and adipogenic differentiation ability by induction. The positive expression rates of CD29 and CD44 were higher than 90.00%. The cells were identified as ADSCs. After 28 days of injection, the collagen fibers in the dermis of skin tissue at the injection area of rats in blank control group were finely arranged. In simple scar group, a large amount of collagen was deposited in the dermis of skin tissue at the injection area of rats, the fiber bundles were thick and loosely unevenly arranged, and a large number of inflammatory infiltration and scattered muscle fibers were observed. In ADSCs transplantation group, the collagen fibers in the dermis of skin tissue at the injection area of rats were thicker than those of blank control group, with still neat arrangement, and a small amount of scattered muscle fiber and inflammatory infiltration was observed. After 28 days of injection, the expression of α-SMA in ADSCs transplantation group was mainly in microvessels in the dermis of skin tissue at the injected area of rats, and the number of α-SMA and TGF-ß(1) positive cells was (49±12) and (63±10) cells per 20-fold field of view, respectively, which was similar to (35±16) and (44±17) cells per 20-fold field of view of blank control group (P>0.05), all significantly less than (135±13) and (121±23) cells per 20-fold field of view of simple scar group (P<0.05). Conclusions: Compared with those of autologous simple granule fat transplantation, autologous nano-fat mixed granule fat transplantation has better filling fullness in the treatment of patients with scar facial depression and atrophy. The filling effect lasts longer, and the improvement of scar texture is more obvious. As showed in the rat scar model experiment, the mechanism may be that ADSCs inhibit the expressions of α-SMA and TGF-ß(1), thus inhibiting the formation of scar.

Artificial Gauge Field and Topological Phase in a Conventional Two-dimensional Electron Gas with Antidot Lattices.

Based on the Born-Oppemheimer approximation, we divide the total electron Hamiltonian in a spin-orbit coupled system into the slow orbital motion and the fast interband transition processes. We find that the fast motion induces a gauge field on the slow orbital motion, perpendicular to the electron momentum, inducing a topological phase. From this general designing principle, we present a theory for generating artificial gauge field and topological phase in a conventional two-dimensional electron gas embedded in parabolically graded GaAs/InxGa1-xAs/GaAs quantum wells with antidot lattices. By tuning the etching depth and period of the antidot lattices, the band folding caused by the antidot potential leads to the formation of minibands and band inversions between neighboring subbands. The intersubband spin-orbit interaction opens considerably large nontrivial minigaps and leads to many pairs of helical edge states in these gaps.