MicroRNA-146a-5p induces cell cycle arrest and enhances apoptosis in gastric cancer via targeting CDC14A.

Objective: The present study was designed to investigate the expression of miRNA-146a-5p in gastric cancer (GC) tissues and the paired nonmalignant counterparts, to explore the influences of miRNA-146a-5p on the cell biological behavior of MKN-28 cells (highly metastatic human gastric cancer cells), and to identify the function of abnormal expression of its target gene cell division cycle 14 homolog A (CDC14A) in GC. Methods: We detected the expression of miRNA-146a-5p in formalin-fixed and paraffin-embedded (FFPE) GC tissues through microarray and quantitative real-time polymerase chain reaction (qRT-PCR). Then, we employed cell counting kit-8 (CCK-8) assays, cell cycle assays, and apoptosis analysis to uncover the latent function of miRNA-146a-5p in MKN-28 human GC cells. We also validated the target of miRNA-146a-5p via luciferase reporter assays. Results: miRNA-146a-5p levels were examined in the majority of primary GC tissues and several GC cell lines. As a result, miRNA-146a-5p levels were significantly declined in the GC tissues and cells. In addition, miRNA-146a-5p demonstrated a straight act on its 3'-untranslated region (3'-UTR) of CDC14A mRNA, accordingly decreasing the contents of CDC14A mRNA as well as its protein expression. An inverse correlation between CDC14A and miRNA-146a-5p was observed. Conclusion: The data suggest miRNA-146a-5p may contribute to inducing cell cycle arrest as well as prompting GC cell apoptosis via directly targeting CDC14A. Therefore, miRNA-146a-5p may be a potential indicator of the occurrence and development of GC.

New insights into nanosystems for non-small-cell lung cancer: diagnosis and treatment.

Lung cancer is caused by a malignant tumor that shows the fastest growth in both incidence and mortality and is also the greatest threat to human health and life. At present, both in terms of incidence and mortality, lung cancer is the first in male malignant tumors, and the second in female malignant tumors. In the past two decades, research and development of antitumor drugs worldwide have been booming, and a large number of innovative drugs have entered clinical trials and practice. In the era of precision medicine, the concept and strategy of cancer from diagnosis to treatment are experiencing unprecedented changes. The ability of tumor diagnosis and treatment has rapidly improved, the discovery rate and cure rate of early tumors have greatly improved, and the overall survival of patients has benefited significantly, with a tendency to transform to a chronic disease with tumor. The emergence of nanotechnology brings new horizons for tumor diagnosis and treatment. Nanomaterials with good biocompatibility have played an important role in tumor imaging, diagnosis, drug delivery, controlled drug release, etc. This article mainly reviews the advancements in lipid-based nanosystems, polymer-based nanosystems, and inorganic nanosystems in the diagnosis and treatment of non-small-cell lung cancer (NSCLC).

Multidisciplinary team diagnosis and treatment of pancreatic cancer: Current landscape and future prospects.

The pathogenesis of pancreatic cancer has not been completely clear, there is no highly sensitive and specific detection method, so early diagnosis is very difficult. Despite the rapid development of tumor diagnosis and treatment, it is difficult to break through in the short term and the overall 5-year survival rate of pancreatic cancer is less than 8%. In the face of the increasing incidence of pancreatic cancer, in addition to strengthening basic research, exploring its etiology and pathogenesis, it is urgent to optimize the existing diagnosis and treatment methods through standard multidisciplinary team (MDT), and formulate personalized treatment plan to achieve the purpose of improving the curative effect. However, there are some problems in MDT, such as insufficient understanding and enthusiasm of some doctors, failure to operate MDT according to the system, lack of good communication between domestic and foreign peers, and lack of attention in personnel training and talent echelon construction. It is expected to protect the rights and interests of doctors in the future and ensure the continuous operation of MDT. To strengthen the research on the diagnosis and treatment of pancreatic cancer, MDT can try the Internet +MDT mode to improve the efficiency of MDT.

SP1 transcriptionally regulates UBE2N expression to promote lung adenocarcinoma progression.

Lung adenocarcinoma (LUAD) is the main cause of cancer-related death worldwide. Understanding the mechanisms of LUAD progression may provide insights into targeted therapy approaches for this malignancy. Ubiquitin-conjugating enzyme 2 N (UBE2N) has been demonstrated to play key roles in the progression of various cancers. However, the functions and mechanisms underlying UBE2N expression in LUAD are still unclear. In this study, we found that UBE2N is highly expressed in LUAD and patients with high UBE2N expression in their tumors have poor clinical outcomes. Moreover, we showed that UBE2N interference significantly inhibited LUAD progression in vitro and in vivo. At the molecular level, we demonstrated that the UBE2N is a bona fide target of transcription factor SP1. SP1 directly bound to the promoter of UBE2N and upregulated its expression in LUAD cells, which in turn contributed to the progression of LUAD. Furthermore, we found that there is a strong positive correlation between the expression of SP1 and UBE2N in LUAD samples. Importantly, LUAD patients with concomitantly high expression of SP1 and UBE2N were significantly associated with poor clinical outcomes. In conclusion, our study demonstrated that the SP1-UBE2N signaling axis might play a key role in the malignant progression of LUAD, which provides new targets and strategies for the treatment of LUAD.

Advances and challenges of immunocheckpoint inhibitors in the treatment of primary liver cancer.

Primary liver cancer (PLC) is one of the most common malignant tumors, which clinically characterized by occult onset, rapid development, easy recurrence and poor prognosis. With the rapid development of tumor immunotherapy research, tumor immunotherapy has also achieved remarkable clinical efficacy, and jointly promoted the overall improvement of tumor immunology from mechanism research to clinical transformation, from single discipline to multi-disciplinary integration. Immunotherapy has obvious advantages in treatment-related toxicity and efficacy compared with traditional therapy. In hepatocellular carcinoma (HCC), immunotherapy alone or in combination with other therapies may help to control tumor progression, and there are many immune checkpoint inhibitors (ICIs) widely used in clinical or ongoing clinical trials. However, tumor immunology research is still facing many challenges. How to effectively evaluate the efficacy, whether there are related biomarkers, the generation of immune tolerance and the lack of clinical trials to objectively evaluate the efficacy are still urgent problems to be solved, but it also brings new research opportunities for basic and clinical immunology researchers. The study of treatment of ICIs of PLC has become a hot spot in clinical research field. This paper summarizes and prospects the research progress and challenges of ICIs for PLC.

Diagnosis and Treatment of Rheumatic Adverse Events Related to Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) have completely changed the treatment of cancer, and they also can cause multiple organ immune-related adverse reactions (irAEs). Among them, rheumatic irAE is less common, mainly including inflammatory arthritis, rheumatic myalgia/giant cell arteritis, inflammatory myopathy, and Sjogren's syndrome. For oncologists, rheumatism is a relatively new field, and early diagnosis and treatment is very important, and we need to work closely with experienced rheumatologists. In this review, we focused on the incidence, clinical characteristics, and treatment strategies of rheumatic irAE.

Differentiating pneumonia with and without COVID-19 using chest CT images: from qualitative to quantitative.

BACKGROUND: Pneumonia caused by COVID-19 shares overlapping imaging manifestations with other types of pneumonia. How to objectively and quantitatively differentiate pneumonia patients with and without COVID-19 virus remains clinical challenge. OBJECTIVE: To formulate standardized scoring criteria and an objective quantization standard to guide decision making in detection and diagnosis of COVID-19 virus induced pneumonia in clinical practice. METHODS: A retrospective dataset includes computed tomography (CT) images acquired from 43 pneumonia patients with COVID-19 virus detected by reverse transcription-polymerase chain reaction (RT-PCR) tests and 49 pneumonia patients without COVID-19 virus. All patients were treated during the same time period in two hospitals. Key indicators of differential diagnosis were identified in relevant literature and the scores were quantified namely, patients with more than 8 points were identified as high risk, those with 6-8 points as moderate risk, and those with fewer than 6 points as low risk for COVID-19 virus. In the study, 3 radiologists determined the scores for all patients. Diagnostic sensitivity and specificity were subsequently calculated. RESULTS: A total of 61 patients were determined as high risk, among which 42 were COVID-19 positive by RT-PCR tests. Next, 9 were identified as moderate risk, one of whom was COVID-19 positive. Last, 22 were classified into the low-risk group, all of them are COVID-19 negative. Based on these results, the sensitivity of detection COVID-19 positive cases between the high-risk group and the non-high-risk group was 0.98 with 95% confidence interval [0.88, 1.00], and the specificity was 0.61 [0.46, 0.75]. The detection sensitivity between the moderate-/high-risk group and the low-risk group was 1.00 [0.92, 1.00], and the specificity was 0.45 [0.31, 0.60]. CONCLUSION: The proposed quantitative scoring criteria showed high sensitivity and moderate specificity in detecting COVID-19 using CT images, which indicates that these criteria may be beneficial for screening in real-world practice and helpful for long-term disease control.

Effectiveness of a combination therapy of traditional Chinese medicine and CO2 laser treatment for condyloma acuminatum.

BACKGROUND: Condyloma acuminatum (CA) is both highly infectious and frequently recurring and requires long-term, repeated treatments, which seriously affect the physical and psychological health of patients. The purpose of the present study was to investigate the effectiveness of a combination therapy of traditional Chinese medicine and CO2 laser on CA and the relationship between CA relapse and cellular immunity. METHODS: The study cohort consisted of 160 CA patients who underwent ambulatory treatment between January 2017 and January 2019 in the Department of Dermatology and Venerology of our hospital. The 160 patients were randomly divided into two groups: a combination therapy group (80 cases), who underwent CO2 -laser treatment followed by three courses of oral traditional Chinese medicine and a control group (80 cases), who were only treated with the CO2 laser to remove warts. The efficacy of the CO2 -laser treatment was evaluated on the first month after treatment and relapse was evaluated at monthly follow-ups for 6 months. Additionally, 20 normal volunteers were also recruited. Three months before and after treatment, the cellular immunity factors of peripheral blood T lymphocyte subsets, including CD4+, CD8+, CD4+/CD8+, and interleukin-2 (IL-2), were detected and compared between CA patients and normal volunteers, the combination therapy and control groups, and the relapse and cure groups to determine whether there were statistical differences. RESULTS: Compared with normal volunteers, CA patients exhibited lower CD4+, CD4+/CD8+, and IL-2 levels and higher CD8+ levels (P < .05). In addition, the rates of relapse for the combination therapy and control groups were 25.7% and 40.8%, respectively. However, the comprehensive immunity factors showed no statistical difference (P > .05) before treatment. Three months after treatment, factors including CD4+ and CD4+/CD8+ were higher in the combination therapy group than in the control group (P < .05), and CD8+ and IL-2 showed no statistical difference (P > .05); factors including CD4+, CD4+/CD8+, and IL-2 were higher and CD8+ was lower in the cure group than in the relapse group (P < .05). CONCLUSION: The therapy combination of traditional Chinese medicine and CO2 -laser treatment can reduce the relapse rate of CA. It might be that traditional Chinese medicine combined with CO2-laser treatment regulate liver meridian, Qi and blood, and restore the balance between various subgroups.

Diagnosis of the Coronavirus disease (COVID-19): rRT-PCR or CT?

PURPOSE: To evaluate the diagnostic value of computed tomography (CT) and real-time reverse-transcriptase-polymerase chain reaction (rRT-PCR) for COVID-19 pneumonia. METHODS: This retrospective study included all patients with COVID-19 pneumonia suspicion, who were examined by both CT and rRT-PCR at initial presentation. The sensitivities of both tests were then compared. For patients with a final confirmed diagnosis, clinical and laboratory data, in addition to CT imaging findings were evaluated. RESULTS: A total of 36 patients were finally diagnosed with COVID-19 pneumonia. Thirty-five patients had abnormal CT findings at presentation, whereas one patient had a normal CT. Using rRT-PCR, 30 patients were tested positive, with 6 cases initially missed. Amongst these 6 patients, 3 became positive in the second rRT-PCR assay(after 2 days, 2 days and 3 days respectively), and the other 3 became positive only in the third round of rRT-PCR tests(after 5 days, 6 days and 8 days respectively). At presentation, CT sensitivity was therefore 97.2%, whereas the sensitivity of initial rRT-PCR was only 83.3%. CONCLUSION: rRT-PCR may produce initial false negative results. We suggest that patients with typical CT findings but negative rRT-PCR results should be isolated, and rRT-PCR should be repeated to avoid misdiagnosis.

2019 Novel Coronavirus (COVID-19) Pneumonia: Serial Computed Tomography Findings.

From December 2019, Coronavirus disease 2019 (COVID-19) pneumonia (formerly known as the 2019 novel Coronavirus [2019-nCoV]) broke out in Wuhan, China. In this study, we present serial CT findings in a 40-year-old female patient with COVID-19 pneumonia who presented with the symptoms of fever, chest tightness, and fatigue. She was diagnosed with COVID-19 infection confirmed by real-time reverse-transcriptase-polymerase chain reaction. CT showed rapidly progressing peripheral consolidations and ground-glass opacities in both lungs. After treatment, the lesions were shown to be almost absorbed leaving the fibrous lesions.

Capture and biological release of circulating tumor cells in pancreatic cancer based on peptide-functionalized silicon nanowire substrate.

BACKGROUND: Efficient and precise circulating tumor cells' (CTCs) capture and release with minimal effect on cell viability for CTCs' analysis are general requirements of CTCs' detection device in clinical application. However, these two essential factors are difficult to be achieved simultaneously. METHODS: In order to reach the aforementioned goal, we integrated multiple strategies and technologies of staggered herringbone structure, nanowires' substrate, peptides, enzymatic release, specific cell staining, and gene sequencing into microfluidic device and the sandwich structure peptide-silicon nanowires' substrate was termed as Pe-SiNWS. RESULTS: The Pe-SiNWS demonstrated excellent capture efficiency (95.6%) and high release efficiency (92.6%). The good purity (28.5%) and cell viability (93.5%) of CTCs could be obtained through specific capture and biological release by using Pe-SiNWS. The good purity of CTCs facilitated precise and quick biological analysis, and five types of KRAS mutation were detected in 16 pancreatic cancer patients but not in healthy donors. CONCLUSION: The results proved that the effective capture, minor damage release, and precise analysis of CTCs could be realized simultaneously by our novel strategy. The successful clinical application indicated that our work was anticipated to open up new opportunities for the design of CTC microfluidic device.

Detecting EGFR mutations and ALK/ROS1 rearrangements in non-small cell lung cancer using malignant pleural effusion samples.

BACKGROUND: The study was conducted to evaluate the feasibility of using malignant pleural effusion (MPE) as a substitute specimen for genetic testing and to determine the significance of genetic profiling of MPE tumor cells to monitor non-small cell lung cancer (NSCLC) progression and therapeutic response. METHODS: We selected 168 NSCLC patients with MPE. We extracted MPE and enriched tumor cells using a custom-designed device. EGFR mutations and ALK/ROS1 fusions were then detected by quantitative real-time PCR, and the results were used to guide targeted therapy. We investigated drug responses through imaging. RESULTS: MPE tumor cells were detected in all patients. EGFR mutations and ALK/ROS1 rearrangements were detected in biopsy samples, treated MPE, and untreated MPE. We found that treated MPE had higher sensitivity and specificity than biopsy or untreated MPE. Among the 26 EGFR inhibitor patients, 13 showed a partial response, 7 had progressive disease, and 6 showed stable disease. Among the 16 patients that received ALK/ROS1 inhibitors, 8 had a partial response, 4 had progressive disease, and 4 showed stable disease. CONCLUSION: Our study provides a new, less invasive, and highly repeatable method of analyzing MPE tumor cells in NSCLC that facilitates precision medicine and genetic testing.

Wogonin improves functional neuroprotection for acute cerebral ischemia in rats by promoting angiogenesis via TGF-ß1.

BACKGROUND: Previous studies showed that wogonin is a potential candidate for more effective treatment of neuronal and inflammatory disease and could offer neuroprotective activity in various models, but all these studies were in vitro. Our research aimed to investigate the neuroprotective effect of wogonin on focal cerebral ischemia in rats and uncover its potential mechanism. METHODS: A total of 80 male SD rats were randomly divided into a sham operation group (Sham group, 20 rats), a normal saline group (NS group, 20 rats), and a wogonin intervention group (W2W group, 20 rats), while the remaining 20 rats were kept as a substitute. The model of focal cerebral ischemia (MCAO) was established by thread embolization. The neurological deficits were evaluated by the modified neurological deficit scale (mNSS). The laser confocal technique was used to observe the diameter, density, and total area of microvessel. Lastly, the expression of transforming growth factor-ß1 (TGF-ß1) was detected by Western blot. RESULTS: The mNSS scores of the NS group and Wn2W group were 6.57±1.13 and 4.39±0.92 respectively, and the difference between NS group and Wn2W group was statistically significant (P<0.05); the vascular diameter of the Wn2W group, Sham group, and NS group were 2.93±0.19, 4.24±0.16, and 3.56±0.22 µm respectively, and the differences among these groups were statistically significant (F=102.142, P<0.01). Furthermore, the differences in the vascular density (F=290.49, P<0.01) and total microvessel area (F=163.08, P<0.01) among these groups were also statistically significant. The expression of TGF-ß1 in ischemic brain tissue of the Sham group, NS group, and Wn2W group were 0.46±0.14, 0.62±0.18, and 0.94±0.21 respectively, and the differences among these groups were statistically significant (F=102.142, P<0.01). CONCLUSIONS: Wogonin can markedly reduce nerve injury and improve nerve function in rats with cerebral ischemia, which may be related to the TGF-ß1 pathway.

Aptamer-polymer functionalized silicon nanosubstrates for enhanced recovered circulating tumor cell viability and in vitro chemosensitivity testing.

Selection of the optimal chemotherapy regimen for an individual cancer patient is challenging. The existing chemosensitivity tests are costly, time-consuming, and not amenable to wide utilization within a clinic. This limitation might be addressed by the recently proposed use of circulating tumor cells (CTCs), which provide an opportunity to noninvasively monitor response to therapy. Over the past few decades, various techniques were developed to capture and recover CTCs, but these techniques were often limited by a capture and recovery performance tradeoff between high viability and high efficiency. In this work, we used anti-epithelial cell adhesion molecule coated aptamer-poly (N-isopropylacrylamide) functionalized silicon nanowire substrates to capture and release epithelial cell adhesion molecule-positive CTCs at 32°C and 4°C, respectively. Then, we applied the nuclease to digest the aptamer to release the captured CTCs (near or at the end of the polymer brush), which cannot be released by heating/cooling process. High viability and purity CTCs could be achieved by decreasing the heating/cooling cycles and enzymatic treatment rounds. Furthermore, the time-saving process is helpful to maintain the morphology and enhance vitality of the recovered CTCs and is beneficial to the subsequent cell culture in vitro. We validated the feasibility of chemosensitivity testing based on the recovered HCC827 cells using an adenosine triphosphate-tumor chemosensitivity assay, and the results suggested that our method can determine which agent and what concentration have the best chemosensitivity for the culturing recovered CTCs. So, the novel method capable of a highly effective capture and recovery of high viability CTCs will pave the way for chemosensitivity testing.

NanoVelcro Chip for CTC enumeration in prostate cancer patients.

Circulating tumor cells (CTCs) are one of the most crucial topics in rare cell biology and have become the focus of a significant and emerging area of cancer research. While CTC enumeration is a valid biomarker in prostate cancer, the current FDA-approved CTC technology is unable to detect CTCs in a large portion of late stage prostate cancer patients. Here we introduce the NanoVelcro CTC Chip, a device composed of a patterned silicon nanowire substrate (SiNW) and an overlaid polydimethylsiloxane (PDMS) chaotic mixer. Validated by two institutions participating in the study, the NanoVelcro Chip assay exhibits very consistent efficiency in CTC-capture from patient samples. The utilized protocol can be easily replicated at different facilities. We demonstrate the clinical utility of the NanoVelcro Chip by performing serial enumerations of CTCs in prostate cancer patients after undergoing systemic therapy. Changes in CTC numbers after 4-10 weeks of therapy were compared with their clinical responses. We observed a statistically significant reduction in CTCs counts in the clinical responders. We performed long-term follow up with serial CTC collection and enumeration in one patient observing variations in counts correlating with treatment response. This study demonstrates the consistency of the NanoVelcro Chip assay over time for CTC enumeration and also shows that continuous monitoring of CTC numbers can be employed to follow responses to different treatments and monitor disease progression.

High-purity prostate circulating tumor cell isolation by a polymer nanofiber-embedded microchip for whole exome sequencing.

Handpick single cancer cells: a modified NanoVelcro Chip is coupled with ArcturusXT laser capture microdissection (LCM) technology to enable the detection and isolation of single circulating tumor cells (CTCs) from patients with prostate cancer (PC). This new approach paves the way for conducting next-generation sequencing (NGS) on single CTCs.

Capture and stimulated release of circulating tumor cells on polymer-grafted silicon nanostructures.

A platform for capture and release of circulating tumor cells is demonstrated by utilizing polymer grafted silicon nanowires. In this platform, integration of ligand-receptor recognition, nanostructure amplification, and thermal responsive polymers enables a highly efficient and selective capture of cancer cells. Subsequently, these captured cells are released upon a physical stimulation with outstanding cell viability.