A novel amplifier system was proposed for low-noise recording of pico-ampere current in nanopore experiment (<100 pA). As an example, the amplifier system was applied in α-hemolysin based nanopore detection of DNA-PEG-DNA conjugate to record the signals of translocation and bumping events in buffer solution (1 mol/L KCl, 10 mmol/L Tris--HCl, 1 mmol/L EDTA and pH=8. 0). The amplified current signal was filtered by a 3 kHz Bessel filter and sampled by a 100 kHz analog-digital convertor. As a result, the presented amplifier system could lower the noise in recording the current. The current blockages (<10 pA) of single molecules with low amplitude were recovered due to the high signal-to-noise ratio.

Hepatocellular carcinoma (HCC) frequently presents as advanced stage with poor prognosis and high mortality. Systemic treatment is the treatment of choice for advanced disease. In 2007, the first multi-kinase inhibitor (MKI) sorafenib was approved and shown to modestly prolong overall survival (OS). The progress of systemic therapy has been slow afterwards until 2018 when lenvatinib, another MKI, was shown to be non-inferior to sorafenib on median OS as the first-line therapy for HCC. Since then, remarkable progress has been achieved on the treatment of advanced HCC, including the development of second-line targeted treatment, including regorafenib, cabozantinib and ramucirumab from 2017 to 2019. A growing focus has been placed on immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1), its ligand PD-L1, and cytotoxic T-lymphocyte-associated protein 4. These ICIs have proven their potency in treating HCC as both initial and subsequent line of therapy. At present, both regimens of atezolizumab combined with bevacizumab, as well as the combination of tremelimumab and durvalumab, are recommended as the first-line treatments based on positive phase III clinical trials. With the advancement of ICIs, it is anticipated that the role of MKIs in the treatment of HCC will evolve. In this article, lenvatinib, one of the most commonly used MKIs in HCC, is chosen to be reviewed.

OBJECTIVE: To determine the expression of DLK1 gene in acute leukemias (AL) and its function in erythroid differentiation of K562 cells. METHODS: We detected the expression of DLK1 gene in 65 different acute leukemia categories (a test group) and 34 normal bone marrow controls (a control group) with RT-PCR. DLK1 protein in 20 out of the 65 AL patients and 13 of the 34 controls was assayed by Western blot. The K562 cell line was induced to erythroid differentiation by hemin. We observed the relationship between its expression and erythroid differentiation. RESULTS: Both leukemia cells and normal marrow cells expressed DLK1. The expression of DLK1 mRNA in patients in the test group was higher than that in the control group (P=0.018), while there was no significance between acute lymphoblastic leukemia and acute myelogenous leukemia (P>0.05).The expression of DLK1 mRNA in the test group at onset had no relation with the WBC and platelet count in the total peripheral blood, and the same was true for blast cell rates in bone marrow cells.The level of DLK1 protein in the test group was higher than that in the control group, which was consistent with the mRNA expression (P=0.042). The expression of DLK1 mRNA decreased gradually with K562 cells towards hemin-induced erythroid differentiation. CONCLUSION DLK1 gene may be involved in leukemia,but the mRNA level of DLK1 has no relation with some clinical characteristics of AL patients at onset. DLK1 may inhibit the erythroid differentiation of K562 cells.
Acute Disease ; Adolescent ; Adult ; Aged ; Calcium-Binding Proteins ; Case-Control Studies ; Cell Differentiation ; drug effects ; genetics ; Cell Transformation, Neoplastic ; genetics ; Child ; Child, Preschool ; Erythroid Cells ; pathology ; Erythroid Precursor Cells ; pathology ; Female ; Humans ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; K562 Cells ; Leukemia ; genetics ; metabolism ; Male ; Membrane Proteins ; genetics ; metabolism ; Middle Aged ; RNA, Messenger ; genetics ; metabolism ; Young Adult

We report computed tomography (CT) findings for a rare case of follicular dendritic cell sarcoma of the greater omentum from a 47-year-old female patient. The tumor presented ash a palpable mass lesion in the umbilical region for the last two months. Multidetector CT scan of the abdomen showed a 14-cm soft-tissue mass with calcification and necrosis within the greater omentum. As a result, a follicular dendritic cell sarcoma should be considered in the differential diagnosis of a solitary omentum mass, especially one with coarse and chunk-like calcifications.
Dendritic Cell Sarcoma, Follicular/pathology/*radiography ; Female ; Humans ; Middle Aged ; Multidetector Computed Tomography/*methods ; Omentum/pathology/*radiography ; Peritoneal Neoplasms/pathology/*radiography

Objective To investigate the relationship between the phenotypes and the patterns of genetic mutations in the corresponding resistance genes (rpoB, katG, inhA, ahpC, rrs, rpsL, embB and gyrA) in resistant Mycobacterium tuberculosis (MTB) isolates. Methods Rifampicin-resistant gene (rpoB), isoniazid-resistant genes (katG, inhA, ahpC), streptomycin-resistant genes (rrs, rpsL), ethambutol-resistant gene (embB) and quinolinone-resistant gene (gyrA) were amplified by PCR with sequence-specific primers, then mutants screened by single-stranded conformation polymorphism (SSCP) were sequenced. Results rpoB mutation with predominant Ser450Trp pattern was 94. 9% (56/59) in 59 rifampicin-resistant isolates;katG mutation rate was 38. 9% (35/90) and the main pattern was Ser315Thr, but only 3 inhA mutants and no ahpC mutation were determined in 90 isoniazid-resistant isolates;gyrA mutation with main Asp94Gly then Ala90Val pattern was 82.4% (28/34) in 34 quinolinone-resistant isolates;the total mutation rate was 77.4% in 31 streptomycin-resistant isolates, of which 15 isolates mutated in rrs with main pattern A514C or A1041G, 10 isolates mutated in rpsL Lys88Arg;and embB mutation with main Met306Val accounted for 19.4% (6/31) in 31 ethambutol-resistant isolates. Conclusions The results showed that resistance of resistant MTB may be complicated, and DNA sequencing-based mutation analysis could efficiently detect the molecular makers such as rpoB, katG, gyrA, rrs, rpsL and embB in resistant MTB isolates. Meanwhile, it is notable that the rpoB mutation pattern in our isolates is different from previous report, further effort are needed to confirm the characteristics. The spectrum of potential resistance-related mutations in MTB clinical isolates may lay substantial foundation for the rapid molecular diagnosis and rational use of drug to MTB patients.

Retaining or improving periodontal ligament (PDL) function is crucial for restoring periodontal defects. The aim of this study was to evaluate the physiological effects of low-power laser irradiation (LPLI) on the proliferation and osteogenic differentiation of human PDL (hPDL) cells. Cultured hPDL cells were irradiated (660 nm) daily with doses of 0, 1, 2 or 4 J⋅cm(-2). Cell proliferation was evaluated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, and the effect of LPLI on osteogenic differentiation was assessed by Alizarin Red S staining and alkaline phosphatase (ALP) activity. Additionally, osteogenic marker gene expression was confirmed by real-time reverse transcription-polymerase chain reaction (RT-PCR). Our data showed that LPLI at a dose of 2 J⋅cm(-2) significantly promoted hPDL cell proliferation at days 3 and 5. In addition, LPLI at energy doses of 2 and 4 J⋅cm(-2) showed potential osteogenic capacity, as it stimulated ALP activity, calcium deposition, and osteogenic gene expression. We also showed that cyclic adenosine monophosphate (cAMP) is a critical regulator of the LPLI-mediated effects on hPDL cells. This study shows that LPLI can promote the proliferation and osteogenic differentiation of hPDL cells. These results suggest the potential use of LPLI in clinical applications for periodontal tissue regeneration.
Adenine ; analogs & derivatives ; pharmacology ; Adenylyl Cyclase Inhibitors ; Alkaline Phosphatase ; analysis ; genetics ; radiation effects ; Anthraquinones ; Bone Morphogenetic Protein 2 ; genetics ; Calcium ; metabolism ; radiation effects ; Cell Culture Techniques ; Cell Differentiation ; radiation effects ; Cell Line ; Cell Proliferation ; radiation effects ; Coloring Agents ; Core Binding Factor Alpha 1 Subunit ; genetics ; Cyclic AMP ; antagonists & inhibitors ; radiation effects ; Gene Expression ; radiation effects ; Humans ; L-Lactate Dehydrogenase ; analysis ; Lasers, Semiconductor ; Low-Level Light Therapy ; instrumentation ; Osteocalcin ; genetics ; Osteogenesis ; genetics ; radiation effects ; Periodontal Ligament ; cytology ; radiation effects ; Radiation Dosage ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Tetrazolium Salts ; Thiazoles

PURPOSE: The purpose of this study was to compare preoperative clinical outcomes before occurrence of periprosthetic femoral fracture (status before trauma) with postoperative clinical outcomes (status after operation) in patients with periprosthetic femoral fracture after hip arthroplasty. MATERIALS AND METHODS: A retrospective review was performed of all periprosthetic femoral fracture after hip arthroplasty treated surgically at our institution from January 2010 to January 2014. Among 29 patients who underwent surgical treatment for periprosthetic femoral fracture after hip arthroplasty, 3 patients excluded because of non-union of the fracture site. The clinical outcomes were determined by using visual analogue scale for pain (VAS), Harris hip score (HHS), and ambulatory ability using Koval classification. VAS, HHS and ambulatory ability was assessed for all the included patients at the last follow-up of status before trauma and after operation. RESULTS: The mean VAS, HHS and ambulatory ability at the last follow-up of status before trauma was 2.2 (range, 0-4), 78.9 (range, 48-92) and 1.9 (range, 1-5), respectively. The mean VAS, HHS and ambulatory ability at the last follow-up of status after operation was 3.1 (range, 1-5), 68.4 (range, 46-81) and 2.9 (range, 2-6), respectively. The clinical outcome of VAS, HHS and ambulatory ability were significantly worsened after surgical treatment for periprosthetic femoral fracture (P=0.010, P=0.001, and P=0.002, respectively). CONCLUSION: Patients with periprosthetic femoral fracture after hip arthroplasty could not return to their status before trauma, although patients underwent appropriate surgical treatment and the fracture union achieved.
Arthroplasty* ; Classification ; Femoral Fractures* ; Follow-Up Studies ; Hip* ; Humans ; Periprosthetic Fractures ; Retrospective Studies

OBJECTIVETo investigate the expression variation and significance of Skp2 and p27(kip1) during the proliferation of lymphoma cell line Jurkat cells.

METHODSThe binding of p27(kip1) and Skp2 in Jurkat cells were detected by immunoprecipitation. Jurkat cells were treated with serum starvation and release synchronization. The expression variation and subcellular localization of p27(kip1) and Skp2 were detected by subcellular fractionation, Western blot and double immunofluorescence labelling.

RESULTSThe results of immunoprecipitation suggested that p27(kip1) and Skp2 could bind each other in Jurkat cells. During the proliferation of Jurkat cells, the protein expression of p27(kip1) decreased and intranuclear p27(kip1) decreased significantly, while the Skp2 protein increased and cytoplasmic Skp2 increased significantly.

CONCLUSIONDuring the proliferation of Jurkat cells, the increased cytoplasmic synthesis of Skp2 may speed up p27(kip1) degradation via the ubiquitin-proteasome pathway, then intranuclear p27(kip1) decreases significantly, leading to an increased cell cycling activity.

Cell Nucleus ; metabolism ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p27 ; metabolism ; Cytoplasm ; metabolism ; Humans ; Jurkat Cells ; Lymphoma, B-Cell ; metabolism ; pathology ; Protein Binding ; S-Phase Kinase-Associated Proteins ; metabolism

PURPOSE: This study was designed to compare the wound healing effect of silk fibroin, alginate and fibroin/ alginate blend sponge with clinically used Nu gauze in a rat skin defect model. METHODS: Two full thickness excisions were made on the back of Sprague-Dawley rat. The excised wound was covered with either of the silk fibroin(SF), alginate (SA), or fibroin/alginate blend sponge(SF/SA). On the postoperative days of 3, 7, 10 and 14, the wound area was calculated by image analysis software. At the same time, a skin wound tissue was biopsied. RESULTS: Healing time 50% (HT(50)) of SF/SA sponge treated group was dramatically reduced as compared with that of control treatment. We also found that the HT50 of SF/SA sponge was significantly decreased as compared with either those of SF or SA treatment. Furthermore, SF/SA treatment significantly increased the size of epithelialization and collagen deposition as well as the number of PCNA positive cells on epidermal basement membrane as comapred with those of control treatment. CONCLUSION: Our results suggest that the wound healing effect of SF/SA blend sponge is the best among other treatments including SF and SA during the whole wound healing period.
Animals ; Basement Membrane ; Collagen ; Fibroins ; Porifera* ; Proliferating Cell Nuclear Antigen ; Rats ; Rats, Sprague-Dawley ; Silk* ; Skin ; Skin, Artificial* ; Wound Healing ; Wounds and Injuries*

PURPOSE: The purpose of this study was to determine the prevalence of symptomatic femoroacetabular impingement (FAI) in athletic patients. MATERIALS AND METHODS: From July 2003 to May 2013, 388 patients (422 hips) who underwent arthroscopic surgery for FAI were evaluated demographic characteristics. The patients' age, gender, diagnosis, and type of sports were analyzed using medical records and radiography. RESULTS: Among 422 hips in 388 patients, 156 hips were involved with sports. Among the 156 hips, 86, 43, and 27 hips were categorized as cam, pincer, and mixed type, respectively. Types of sports were soccer, baseball and taekwondo which showed 44, 36 and 35 hips, respectively. Also, cases related to sports according to age were 63 hips for twenties and 12 hips for teenagers in which the two showed highest association to FAI. The kinds of sports that showed high association were 28 hips of soccer and 20 cases of martial arts such as taekwondo and judo for twenties and 9 hips of martial arts for teenagers which was the highest. CONCLUSION: FAI usually occurs in young adults and is highly related to sports activity. Most of the FAI type related to sports activity was cam type, and soccer and martial arts such as taekwondo were the most common cause of it.
Adolescent ; Arthroscopy ; Athletes* ; Baseball ; Diagnosis ; Epidemiology* ; Femoracetabular Impingement* ; Hip ; Humans ; Martial Arts ; Medical Records ; Prevalence ; Radiography ; Soccer ; Sports ; Young Adult