BACKGROUND: Double-stranded RNA-specific adenosine deaminase 1 (ADAR1) binds to double-stranded RNA and catalyzes the deamination of adenosine (A) to inosine (I). The functional mechanism of ADAR1 in non-small cell lung cancer (NSCLC) remains incompletely understood. This study aimed to investigate the prognostic significance of ADAR1 in NSCLC and to elucidate its potential role in regulating tumor cell proliferation and migration. METHODS: Data from The Cancer Genome Atlas (TCGA) and cBioPortal were analyzed to assess the correlation between high ADAR1 expression and clinicopathological features as well as prognosis in lung cancer. We performed Western blot (WB), cell proliferation assays, Transwell invasion/migration assays, and nude mouse xenograft modeling to examine the phenotypic changes and molecular mechanisms induced by ADAR1 knockdown. Furthermore, the ADAR1 p150 overexpression model was utilized to validate the proposed mechanism. RESULTS: ADAR1 expression was significantly elevated in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissues compared with adjacent non-tumor tissues (LUAD: P=3.70×10-15, LUSC: P=0.016). High ADAR1 expression was associated with poor prognosis (LUAD: P=2.03×10-2, LUSC: P=2.81×10-2) and distant metastasis (P=0.003). Gene Set Enrichment Analysis (GSEA) indicated that elevated ADAR1 was associated with mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway activation, matrix metalloproteinase-9 (MMP-9) expression, and cell adhesion. ADAR1 and MMP-9 levels showed a strongly positive correlation (P=6.45×10-34) in 10 lung cancer cell lines, highest in H1581. Knockdown of ADAR1 in H1581 cells induced a rounded cellular morphology with reduced pseudopodia. Concomitantly, it suppressed cell proliferation, invasion, migration, and in vivo tumorigenesis. It also suppressed ERK phosphorylation and downregulated cellular Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog (c-FOS), MMP-9, N-cadherin, and Vimentin. Conversely, ADAR1 p150 overexpression in PC9 cells enhanced ERK phosphorylation and increased c-FOS and MMP-9 expression. CONCLUSIONS High ADAR1 expression is closely associated with poor prognosis and distant metastasis in NSCLC patients. Mechanistically, ADAR1 may promote proliferation, invasion, migration, and tumorigenesis in lung cancer cells via the ERK/c-FOS/MMP-9 axis.
Humans ; Lung Neoplasms/physiopathology* ; Adenosine Deaminase/genetics* ; Matrix Metalloproteinase 9/genetics* ; Cell Proliferation ; Carcinoma, Non-Small-Cell Lung/physiopathology* ; Cell Movement ; Animals ; Mice ; RNA-Binding Proteins/genetics* ; Female ; Male ; Cell Line, Tumor ; Proto-Oncogene Proteins c-fos/genetics* ; Middle Aged ; MAP Kinase Signaling System ; Gene Expression Regulation, Neoplastic ; Mice, Nude ; Extracellular Signal-Regulated MAP Kinases/genetics*

Acupoint is the initial response site of acupuncture stimulus and also the source link of the effect onset of acupuncture. Acupuncture is a mechanical physical stimulus. How is the mechanical force of acupuncture transduced into neuroelectrical and biochemical signals at acupoint? How does the physiochemical information of acupoint launch acupuncture effect? All of these remain the common and crucial questions in the study of acupuncture effect mechanism. Physical changes are induced in the local tissue of acupoint by needling techniques, such as the deformation and displacement of muscle fibers, which may act on the nerve ending receptors and produce electroneurographic signals. Besides, these changes may activate the mechanosensitive ion channels of the cytomembrane in acupoint site. Through cellular signal transduction, the physical signals may be transformed into chemical ones to trigger the physiochemical coupling response of acupoint microenvironment. Eventually, acupuncture effect is generated via nerves and body fluids. "The mechanical force of acupuncture", through "the physiochemical transduction", promotes the body's perception and transmits acupuncture signals. It suggests that acupoint is the "transducer" in the physiochemical information coupling response of acupuncture.
Acupuncture Therapy ; Acupuncture Points

OBJECTIVE: To analyze the factors related to the need for revision surgery due to nonunion or internal fixation failure after the treatment of distal femoral fracture with lateral locking plate (LLP). METHODS: Retrospective analysis was made of the clinical data of 130 cases with distal femoral fracture treated in our hospital from March 2005 to March 2019. SPSS 17.0 software (univariate analysis and Logistic regression analysis) was used to analyze the general condition [gender, age, body mass index (BMI), comorbidities, smoking history], injury related factors (energy of injury, open or closed injury, AO/OTA classification of fracture, fracture area distribution), operation related factors (operation time, reduction quality, postoperative infection) and construct characteristics of internal fixation. RESULTS: Twelve of 130 patients who were included in the study underwent revisional surgery, with a revision rate 9.2%. Univariate analysis showed that there were significant differences in age, BMI, AO/OTA classification, fracture area distribution, operation time, reduction quality, length of plate/fracture area, length of plate/fracture area above condylar between the two groups (P < 0.05). Logistic regression analysis showed that AO/OTA classification (A3), supracondylar involved fracture, operation time, reduction quality and the length of the plate/fracture area above the condylar were the possible related factors (P < 0.05). Destruction of the medial support ability of the femur in comminuted type A3 fracture, supra-condylar cortex area fracture involvement, increase of the bending stress of the LLP due to poor fracture reduction quality, damage of the blood supply of fracture end due to long-time operation, and stress concentration caused by insufficient length of plate might be risk factors of revisional operation after the treatment of distal femoral fracture with LLP. For the patients who needed revision after LLP treatment, additional use of medial minimally invasive plate fixation and autologous bone transplantation, change to intramedullary nail fixation were commonly used clinical treatment strategies. CONCLUSION AO/OTA classification (A3), supracondylar involved fracture, long operation time, poor reduction quality and the length of the plate/fracture area above the condylar were the possible predictive factors of the revision in distal femoral fractures treated with lateral locking plate. The appropriate application of the locking plate and operation strategy are the key to reduce the revision rate in distal femoral fractures.
Humans ; Femoral Fractures/etiology* ; Retrospective Studies ; Femoral Fractures, Distal ; Bone Plates/adverse effects* ; Fracture Fixation, Internal/adverse effects* ; Treatment Outcome

BACKGROUND: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE). METHODS: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE. RESULTS: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively. CONCLUSIONS Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.

OBJECTIVE: To retrospectively analyze the risk factors of avascular necrosis of femoral head (ANFH) after internal fixation in young and mid-aged adults. METHODS: From January 2007 to December 2017, femoral neck fracture patients (18-60 years old) treated by reduction and internal fixation were retrospectively studied in Peking University Third Hospital. We recorded their gender, age, body mass index (BMI), American Society of Anesthesiology (ASA) grade, reason of injury, fracture side, interval between injury and surgery, location of fracture line, Garden classification, Pauwels classification, reduction method (open or closed), internal fixation and reduction quality. The diagnosis of ANFH was confirmed based on X-ray and MRI images during the follow-up. The internal fixation method included cannulated compression screw (CCS) or dynamic hip screw (DHS, with or without anti-rotation screw). χ² test and Logistic regression analysis were used to analyze the relationship between the various factors and postoperative ANFH. RESULTS: A total of 113 patients were included in this study, including 63 males and 50 females with an average age of (43.17 ± 12.34) years. They were followed up by (25.08 ± 16.17) months. ASA grade included grade I (21 cases), grade II (55 cases) and grade III (37 cases). The reasons of injury included low-energy trauma (76 cases) and high-energy (37 cases). The fracture line included subcapital type (37 cases), transverse type (74 cases) and basal type (2 cases). Garden classification included type I (3 cases), type II (46 cases), type III (39 cases) and type IV (25 cases). Pauwels classification included type I (21 cases), type II (55 cases) and type III (37 cases). Interval between injury and surgery was (3.88 ± 3.66) days, 108 patients and 5 patients performed closed and open reduction respectively. 63 patients performed CCS, and 50 patients performed DHS. The reduction quality included grade A (91 cases), grade B (18 cases) and grade C (4 cases). 18 patients developed ANFH after surgery, the incidence rate was 15.93% (18/113). The result of χ² test showed the reason of injury (OR=0.19, P < 0.01), Garden classification (OR=0.13, P < 0.01), Pauwels classification (OR=0.12, P = 0.02), internal fixation method (OR=3.29, P = 0.04) and reduction quality (OR=0.33, P < 0.01) were significantly associated with ANFH. These five factors were further included into the Logistic regression analysis, and its results showed that the reason of injury (OR=4.11, P = 0.03) and Garden classification (OR=4.85, P = 0.04) were statistically significant. CONCLUSION The reason of injury, Garden classification, Pauwels classification, internal fixation and reduction quality may increase the risk of ANFH after surgery, and the reason of injury and Garden classification were much more significant.
Adolescent ; Adult ; Female ; Femoral Neck Fractures ; Femur Head Necrosis ; Fracture Fixation, Internal ; Fracture Healing ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Young Adult

OBJECTIVE: To analyze the risk factors of recurrent kyphosis after removal of short segmental pedicle screw fixation in patients with thoracolumbar burst fractures. METHODS: Retrospective analysis was conducted of 144 cases of thoracolumbar burst fractures without neurological impairment treated in Peking University Third Hospital from January 2010 to December 2017. There were 74 males and 70 females, with an average age of (39.1±13.2) years. The distribution of the injured vertebrae was T12: 42, L1: 72 and L2: 30, with fracture types of A3: 90, B1: 25 and B2: 29. The patients were divided into two groups: Recurrent kyphosis group (n=92) and non-recurrent kyphosis group (n=52). SPSS 26.0 software was used for univariate analysis and Logistic regression analysis. RESULTS: The average follow-up time was 28 (20-113) months. The imaging indexes of pre-operation, 3 days post-operation, 12 months post-operation and the last follow-up were measured and compared. Anterior vertebral body height, segmental kyphosis, vertebral wadge angle and Gardner deformity were significantly improved after operation (P < 0.05), and there were some degrees of loss in the 1-year follow-up; anterior vertebral body height and vertebral wadge angle were no longer changed after the removal of the screws; however, segmental kyphosis and Gardner deformity were still aggravated after the removal of the screws (P < 0.05). There were some degrees of collapse of the height of the upper and lower discs during the follow-up. Univariate analysis showed that there were statistically significant differences (P < 0.05) between the two groups in gender, age (36.9 years vs. 43.0 years), upper disc injury, CT value (174 vs. 160), segmental kyphosis (16.6° vs. 13.3°), vertebral wadge angle (16.7° vs. 13.6°), Gardner deformity (19.1° vs. 15.2°) and ratio of anterior vertebral body height (0.65 vs. 0.71). Logistic regression analysis showed that male (OR: 2.88, 95%CI: 1.196-6.933), upper disc injury (OR: 2.962, 95%CI: 1.062-8.258) and injured vertebral wedge angle were risk factors of recurrent kyphosis after removal of internal fixation for thoracolumbar burst fracture (P < 0.05). CONCLUSION The patients with thoracolumbar burst fracture can obtain satisfactory effect immediately after posterior short segmental pedicle screw fixation, however, there may be some degree of loss during the follow-up. Male, upper disc injury and injured vertebral wedge angle are the risk factors of recurrent kyphosis after removal of internal fixation for thoracolumbar burst fracture.
Adult ; Female ; Fracture Fixation, Internal ; Humans ; Kyphosis/surgery* ; Lumbar Vertebrae/surgery* ; Male ; Middle Aged ; Pedicle Screws ; Retrospective Studies ; Risk Factors ; Spinal Fractures/surgery* ; Thoracic Vertebrae/surgery* ; Treatment Outcome

OBJECTIVETo investigate the presence of leukemia stem cells (LSC) in acute myeloid leukemia (AML) and find out the relative position of leukemia cells in the figures of flow cytometry, and to analyze the relationship between minimal residual diseases (MRD) and the level of LSC, so as to explore the correlation of LSC changes with the curative effect and the prognosis during chemical therapy.

METHODSA total of 85 samples were collected from 50 AML (except M3) patients, including 50 samples from the newly diagnosed patients, 7 samples of AML patients with non-remission and 28 samples of AML patients with complete remission. All samples were used for detection of LSC from immune phenotype of CD34/CD38/CD123 by flow cytometry. The detection of immune phenotypic of leukemia cells was performed in the newly diagnosed patients. The detection of leukemia- associated immune phenotypes (LAIP) was implemented in the non-newly diagnosed patients.

RESULTSThe LSC was identified in the CD34/ CD38/ CD123 in AML and consistent with the relative position of the leukemia cell in flow cytometry figures. Statistical analysis showed significant difference in LSC content between the newly diagnosed AML group and the post-chemotherapy complete remission group(P<0.01),but did not between the newly diagnosed AML group and the post-chemotherapy non-remission group(P>0.05).There was significant positive correlation between the LSC content and MRD level in 28 AML patients with complete remission (r=0.680,P<0.01).

CONCLUSIONLSC exist in AML and the relative position are consistent with the leukemia cells in flow cytometry figures, the size characteristics and weak expression of CD45 are also similar to leukemia cells. The proportion of LSC decreases after chemotherapy. Detecting and tracking the LSC changes in bone marrow and combination with detecting minimal resident disease(MRD) may contribute to evaluate the theraputic efficacy and prognosis of leukemia patients.

Flow Cytometry ; Humans ; Interleukin-3 Receptor alpha Subunit ; Leukemia, Myeloid, Acute ; Neoplasm, Residual ; Neoplastic Stem Cells ; Prognosis

To explore the flavor and meridian tropism classification of Callianthemum taipaicum by principal components analysis(PCA) and partial least square analysis(PLS). Meanwhile,to establish a high performance liquid chromatography-tandem mass spectrometry(HPLC-ESI-MS) method for the simultaneous determination of 55 active components from 13 kinds of Ranunculaceae of Chinese traditional herbs. Samples were separated on HPLC system by Agilent 5 TC-C₁₈（2）（4.6 mm×250 mm，5 μm）column and eluted with acetonitrile and 0.1% formic acid at the flow rate of 0.6 mL·min⁻¹. The data were performed by HPLC-ESI-MS with multiple reaction monitoring（MRM）scanning mode under positive and negative ion modes and quantified by external standards. The data from 13 Ranunculaceae herbs were analyzed by the PLS-tree and cooman's prediction of PCA and PLS to evaluate the similarities and differences of C. taipaicum in flavor and meridian tropism. The results showed that calibration curves of 55 components all showed good linearity, >0.99,with good precision, repeatability and stability. After compared to other 12 herbs,PCA and PLS results revealed that the C. taipaicum belonged to lung and bladder meridians while its flavor attributive to pungent,warm in nature. In conclusion,the analysis approach of chemometric calculation combined with multi-components quantification is suitable for the classification of meridian tropism and flavor of Chinese traditional medicine,which can be used for alternative research of rare herbs.
Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; chemistry ; Mass Spectrometry ; Meridians ; Phytochemicals ; analysis ; Plants, Medicinal ; chemistry ; Ranunculaceae ; chemistry ; Tandem Mass Spectrometry

It's difficult to identify Aucklandiae Radix and Vladimiriae Radix because of their similar composition. In this paper, UPLC method was used to establish their UPLC fingerprint to identify them with the mobile of acetonitrile -0. 05% phosphoric acid water solution by gradient elution at the detection wavelength of 238 nm. Clustering analysis and principal components analysis showed that Vladimiriae Radix was significantly different from Aucklandiae Radix. Eight common peaks and twelve common peaks were defined respectively in Aucklandiae Radix and Vladimiriae Radix herbs by fingerprint analysis. Six of them were identified as syringoside, chlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, costunolide and dehydrocostuslactone by comparing with standard references. There are four peaks in all of Vladimiriae Radix samples and in none of Aucklandiae Radix samples. So UPLC fingerprint can be used to identify these two herbs.
Asteraceae ; chemistry ; classification ; Chromatography, High Pressure Liquid ; Cluster Analysis ; Drugs, Chinese Herbal ; analysis ; chemistry

OBJECTIVETo observe the effect of total flavonoids of Oldenlendia difflusa (FOD) on NF-kappaB and IL-8, TNF-alpha, IL-10 expressions of ulcerative colitis (UC) model rats, and explore its immunological mechanism of anti-UC.

METHODSixty Kunming male mice with the average weight of (20 +/- 2) g were randomly divided into six groups. The control group (cont) was orally administered with distilled water. Whereas the remaining five groups were fed with 4% dextran sulphate sodium (DSS) solution for seven days to induce acute UC, and orally administered with the following drugs: distilled water (for the DSS group), SASP at dose of 500 mg x kg(-1) x d(-1) for the DSS + SASP group, FOD at dose of 60 mg x kg(-1) x d(-1) for the DSS + FOD-H group, FOD at dose of 40 mg x kg(-1) x d(-1) for the DSS + FOD-M group, and FOD at dose of 26.7 mg x kg(-1) x d(-1) for the DSS + FOD-L group. During the modeling and drug administration, the mice were scored for DAI. Seven days later, the mice were put to death, and their colonic tissue samples were collected to evaluate colonic mucosal lesions. The NF-kappaB p65, IL-8, TNF-alpha, IL-10 expressions were tested by immunohistochemical staining and ELISA.

RESULTSeven-day feeding with 4% DSS solution could successfully induce acute UC in mice. Compared with the cont group, the DSS group showed significantly higher DAI and colonic mucosal lesions, remarkable increase in NF-kappaB p65, IL-8, TNF-alpha expression in colonic tissues, and notable decrease in IL-10 expression (P < 0.05). FOD could prevent acute UC in mice included by DSS. Seven-day administration of 60 mg x kg(-1) x d(-1) or 40 mg x kg(-1) x d(-1) FOD could completely or partially resist the above mentioned changes caused by DSS. Compared with the DSS group, the DSS + FOD-H group and the DSS + FOD-M group showed reduction in colonic mucosal lesions, down-regulation in IL-8, TNF-alpha and NF-kappaB p65 expressions and up-regulation in IL-10 expression (P < 0.05).

CONCLUSIONFOD could significantly resist UC in mice. Its mechanism may be related to the inhibition of NF-kappaB p65 activation, the reduction of IL-8 and TNF-alpha expressions and the increase in the anti-inflammatory factor IL-10.

Animals ; Anti-Inflammatory Agents ; administration & dosage ; Colitis, Ulcerative ; drug therapy ; genetics ; immunology ; Drugs, Chinese Herbal ; administration & dosage ; Flavonoids ; administration & dosage ; Humans ; Interleukin-8 ; genetics ; immunology ; Male ; Mice ; NF-kappa B ; genetics ; immunology ; Oldenlandia ; chemistry ; Transcription Factor RelA ; genetics ; immunology ; Tumor Necrosis Factor-alpha ; genetics ; immunology