Hsa-miR-483-5p/mRNA network that regulates chemotherapy resistance in locally advanced rectal cancer identified through plasma exosome transcriptomics.

BACKGROUND: Chemoresistance is the primary contributor to distant metastasis in the context of neoadjuvant chemoradiotherapy (nCRT) for rectal cancer. However, the underlying mechanisms remain elusive. AIM: To detect the differential expression profiles of plasma exosomal microRNAs (miRNAs) in poor and good responders and explore the potential mechanisms of chemoresistance. METHODS: In this study, the profiles of plasma exosomal miRNAs were compared in two dimensions according to treatment responses (poor/good responders) and treatment courses (pre/post-nCRT) using RNA sequencing. RESULTS: Exosome hsa-miR-483-5p was up-regulated in good responders post-nCRT. Bioinformatics analysis revealed that the target genes of hsa-miR-483-5p were mainly enriched in tumor-specific pathways, such as the MAPK signaling pathway, EGFR tyrosine kinase inhibitor resistance, Toll-like receptor signaling pathway, VEGF signaling pathway, and mTOR signaling pathway. Further analysis indicated that MAPK3, RAX2, and RNF165 were associated with inferior recurrence-free survival in patients with rectal cancer, and the profiles of MAPK3, TSPYL5, and ZNF417 were correlated with tumor stage. In addition, the expression profiles of MAPK3, RNF165, and ZNF417 were negatively correlated with inhibitory concentration 50 values. Accordingly, an hsa-miR-483-5p/MAPK3/RNF 165/ZNF417 network was constructed. CONCLUSION: This study provides insights into the mechanism of chemoresistance in terms of exosomal miRNAs. However, further research is required within the framework of our established miRNA-mRNA network.

Microbiological Mechanisms of Collaborative Remediation of Cadmium-Contaminated Soil with Bacillus cereus and Lawn Plants.

Severe cadmium contamination poses a serious threat to food security and human health. Plant-microbial combined remediation represents a potential technique for reducing heavy metals in soil. The main objective of this study is to explore the remediation mechanism of cadmium-contaminated soil using a combined approach of lawn plants and microbes. The target bacterium Bacillus cereus was selected from cadmium-contaminated soil in mining areas, and two lawn plants (Festuca arundinacea A'rid III' and Poa pratensis M'idnight II') were chosen as the target plants. We investigated the remediation effect of different concentrations of bacterial solution on cadmium-contaminated soil using two lawn plants through pot experiments, as well as the impact on the soil microbial community structure. The results demonstrate that Bacillus cereus promotes plant growth, and the combined action of lawn plants and Bacillus cereus improves soil quality, enhancing the bioavailability of cadmium in the soil. At a bacterial suspension concentration of 105 CFU/mL, the optimal remediation treatment was observed. The removal efficiency of cadmium in the soil under Festuca arundinacea and Poa pratensis treatments reached 33.69% and 33.33%, respectively. Additionally, the content of bioavailable cadmium in the rhizosphere soil increased by up to 13.43% and 26.54%, respectively. Bacillus cereus increased the bacterial diversity in the non-rhizosphere soil of both lawn plants but reduced it in the rhizosphere soil. Additionally, the relative abundance of Actinobacteriota and Firmicutes, which have potential for heavy metal remediation, increased after the application of the bacterial solution. This study demonstrates that Bacillus cereus can enhance the potential of lawn plants to remediate cadmium-contaminated soil and reshape the microbial communities in both rhizosphere and non-rhizosphere soils.

Clinical characteristics and risk factors of post-operative intestinal flora disorder following laparoscopic colonic surgery: A propensity-score-matching analysis.

BACKGROUND: Intestinal flora disorder (IFD) poses a significant challenge after laparoscopic colonic surgery, and no standard criteria exists for its diagnosis and treatment. AIM: To analyze the clinical features and risk factors of IFD. METHODS: Patients with colon cancer receiving laparoscopic surgery were included using propensity-score-matching (PSM) methods. Based on the occurrence of IFD, patients were categorized into IFD and non-IFD groups. The clinical characteristics and treatment approaches for patients with IFD were analyzed. Multivariate regression analysis was performed to identify the risk factors of IFD. RESULTS: The IFD incidence after laparoscopic surgery was 9.0% (97 of 1073 patients). After PSM, 97 and 194 patients were identified in the IFD and non-IFD groups, respectively. The most common symptoms of IFD were diarrhea and abdominal, typically occurring on post-operative days 3 and 4. All patients were managed conservatively, including modulation of the intestinal flora (90.7%), oral/intravenous application of vancomycin (74.2%), and insertion of a gastric/ileus tube for decompression (23.7%). Multivariate regression analysis identified that pre-operative intestinal obstruction [odds ratio (OR) = 2.79, 95%CI: 1.04-7.47, P = 0.041] and post-operative antibiotics (OR = 8.57, 95%CI: 3.31-23.49, P < 0.001) were independent risk factors for IFD, whereas pre-operative parenteral nutrition (OR = 0.12, 95%CI: 0.06-0.26, P < 0.001) emerged as a protective factor. CONCLUSION: A stepwise approach of probiotics, vancomycin, and decompression could be an alternative treatment for IFD. Special attention is warranted post-operatively for patients with pre-operative obstruction or early use of antibiotics.

PD-L1 expression guidance on sintilimab versus pembrolizumab with or without platinum-doublet chemotherapy in untreated patients with advanced non-small cell lung cancer (CTONG1901): A phase 2, randomized, controlled trial.

No direct comparison has been performed between different programmed cell death-1 (PD-1) inhibitors for first-line treatment in patients with advanced non-small cell lung cancer (NSCLC). The feasibility of using PD-L1-expression-guided immunotherapy remains unknown. In this open-label, phase 2 study (NCT04252365), patients with advanced NSCLC without EGFR or ALK alterations were randomized (1:1) to receive sintilimab or pembrolizumab monotherapy (PD-L1 expression ≥ 50%), or sintilimab or pembrolizumab plus platinum-based chemotherapy (PD-L1 expression < 50%). The sample size was calculated by optimal two-stage design. The primary endpoint was the objective response rate (ORR). The study included 71 patients (sintilimab arms, n = 35; pembrolizumab arms, n = 36) and met its primary endpoint, with a confirmed ORR of 51.4% (18/35) in the sintilimab arms. The confirmed ORR (95% confidence interval) was 46.2% (19.2%, 74.9%) and 42.9% (17.7%, 71.1%) for patients treated with sintilimab and pembrolizumab monotherapy; and 54.5% (32.2%, 75.6%) and 45.4% (24.4%, 67.8%) for those treated with sintilimab- and pembrolizumab-based combination therapies. The median progression-free survival was 6.9 versus 8.1 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 7.6 versus 11.0 months in monotherapy and 7.4 versus 7.1 months in combination therapies. The median overall survival was 14.9 versus 21.3 months for all sintilimab-treated versus all pembrolizumab-treated patients, respectively, in which it was 14.9 versus 22.6 months in monotherapy and 14.7 versus 17.3 months in combination therapies. Treatment-related adverse events were consistent with safety outcomes of monotherapy and combination therapy in previous phase III studies. However, the incidence of rash was higher with sintilimab than pembrolizumab monotherapy. This is the first prospective phase 2 study to directly compare two anti-PD-1 antibodies as first-line treatment in advanced NSCLC. Sintilimab was efficacious and well-tolerated irrespective of PD-L1 expression level in patients with advanced NSCLC and had similar efficacy and safety to pembrolizumab.

Collagen-EGCG Combination Synergistically Prevents UVB-Induced Skin Photoaging in Nude Mice.

Ultraviolet (UV) radiation is a major cause of skin photoaging through generating excessive oxidative stress and inflammation. One of the strategies is to use photo-chemoprotectors, such as natural products with antioxidant and anti-inflammatory properties, to protect the skin from photo damage. The present study investigates the photoprotective potentials of topical administration of unhydrolyzed collagen, epigallocatechin gallate (EGCG), and their combination against ultraviolet B (UVB)-induced photoaging in nude mice. It is found that both the solo and combined pretreatments could recover UVB-induced depletion of antioxidative enzymes, including superoxide dismutase and glutathione peroxidase (GSH-Px), as well as an increase of lipid peroxide malondialdehyde and inflammatory tumor necrosis factor-α. Meanwhile, the UVB-stimulated skin collagen degradation is attenuated significantly with drug treatments, which is evidenced by expression analysis of matrix metalloproteinase-1 and hydroxyproline. Additionally, the mouse skin histology shows that the drug-pretreated groups possess decreased epidermis thickness and normal collagen fiber structure of the dermis layer. These results demonstrate that both EGCG and collagen can protect the skin against UVB-induced skin photoaging. Synergistically, the combination of them shows the maximum prevention to skin damage, showing its potential in the application of anti-photoaging formulation products.

Expert consensus on clinical research nurse management in China.

Objective: With the rising number of clinical trials conducted in China, the role of Clinical Research Nurses (CRNs) within clinical trial organizations has become increasingly crucial. However, in the absence of industry guidelines, the management of CRNs lacks clarity. This study aims to address this gap by establishing a consensus on CRN management. Methods: The IACRN-Shanghai Chapter assembled a panel of experts to develop a consensus on the management of clinical research nurses. This consensus was formulated through an extensive literature review, expert evaluations, and collaborative conference discussions. Results: The consensus document offers a comprehensive professional definition of CRNs and provides detailed insights into their management. It covers aspects such as job settings, qualifications, responsibilities, training, assessment, workload management, staffing allocation, performance evaluation, and career progression. Conclusions: Establishing a professional definition for CRNs creates a standardized reference point for clinical trial institutions to effectively manage these professionals. Consistency in CRNs' roles, training, staffing, and corresponding assessments is essential for promoting their sustainable and healthy development within the field of clinical research.

Elevated Interleukin-37 Associated with Dengue Viral Load in Patients with Dengue Fever.

Dengue remains a public health issue worldwide. Similar to chronic infectious diseases, stimulation of cytokine production is not enough to drive immune effector cells for effective virus clearance. One possible mechanism is the virus induces a large number of negative stimulatory cytokines inhibiting immune response. Interleukin 37 (IL-37) plays a crucial regulatory role in infection and immunity, inhibits innate and adaptive immunity as an anti-inflammatory cytokine by inhibiting proinflammatory mediators and pathways. To date, there are few studies reporting correlations between dengue fever (DF) and IL-37. In this study we found that the serum IL-37b and IL-37b-producing monocytes in patients were significantly increased in DF patients. A majority of the IL-37b produced by DF patients was produced by monocytes, not lymphocytes. Increased levels of IL-6, IL-10, and IFN-α were also found in DF patients. However, we failed to detect IL-1ß, IL-17A and TNF-α in plasma, because of off-target. In our study, there was no relation between IL-6, IL-10, and IFN-α expressions and IL-37b in serum (P > 0.05). The IL-37b-producing monocytes were negatively correlated with the level of IFN-α in serum and platelet count, and positively correlated with lymphocytes percentage (P < 0.05, respectively). Additionally, serum DENV nonstructural protein 1 levels were positively correlated with monocytes percentages (P < 0.05). Our data represents findings for IL-37b expression and its potential mechanisms in DF patients' immune response.

Current practice for the treatment of obstructive left-sided colon cancer in China: a nationwide cross-sectional survey.

PURPOSE: This study surveyed the current practice of surgical treatment of obstructive left-sided colon cancer (OLCC) in China. METHODS: All colorectal surgery departments at tertiary or secondary hospitals in China were invited to complete a web-based questionnaire between August 27 and September 2, 2020. RESULTS: Overall, completed questionnaire were received from 357 hospitals. Emergency surgery was the mainstay of treatment for OLCC, with the open approach accounting for up to 61.62%. The stoma rate of emergency surgery was up to 80%, mainly due to inadequate bowel preparation and severe edema of colon walls. Hartmann's procedure (61.62%) was the most preferred operation. A total of 243 hospitals (68.7%) reported that they would consider the use of a self-expanding metallic stent (SEMS) as a bridge for elective surgery. More than 50% of the hospitals participating in this study reported the success rate of SEMS placement, as well as the resolution rate of obstruction more than 80%, and the stent-related perforation rate was < 5%. A total of 126 hospitals considered carrying out a strategy of SEMS followed by neoadjuvant chemotherapy prior to elective surgery and believed that it might further improve treatment outcomes. CONCLUSIONS: SEMS is a feasible option for the treatment of OLCC in addition to traditional emergency surgery, and its clinical benefits have been preliminarily recognized.

Case report: The application of neoadjuvant chemoradiotherapy in anal adenocarcinoma combined with perianal Paget disease involving vulvar skin.

Anal adenocarcinoma combined with perianal Paget's disease (PPD) involving the vulva is rare, and there is no established standard treatment. We present the case of a 69-year-old woman with symptoms of intermittent hematochezia and perianal discomfort for 7 months. Upon examination, we discovered a plaque-like hard mass on the right posterior wall of the anal canal, which extended to encompass the anus and dentate line. The lesion skin also extended forward from the gluteal groove, involving the bilateral labial area. Colonoscopy revealed an extensive protruding lesion on the dentate line, which was confirmed as anal adenocarcinoma (mrT4N0M0). The presence of Paget's cells in perianal and vulvar skins led to the diagnosis of PPD. The strategy of neoadjuvant chemoradiotherapy (nCRT) followed by radical surgery was then made after multi-disciplinary discuss. The scope and extent of perianal and vulvar disease were significantly diminished after nCRT. The patient underwent laparoscopic abdominoperineal resection and vulvar lesion resection, confirming the diagnosis of anal adenocarcinoma (ypT2N0). No evidence of tumor cells was found in perianal and vulvar skin, indicating a complete response. The patient is regularly monitored without recurrence or metastasis.

Immunomodulatory roles of selenium nanoparticles: Novel arts for potential immunotherapy strategy development.

Current chemotherapy strategies used in clinic appear with lots of disadvantages due to the low targeting effects of drugs and strong side effects, which significantly restricts the drug potency, causes multiple dysfunctions in the body, and even drives the emergence of diseases. Immunotherapy has been proved to boost the body's innate and adaptive defenses for more effective disease control and treatment. As a trace element, selenium plays vital roles in human health by regulating the antioxidant defense, enzyme activity, and immune response through various specific pathways. Profiting from novel nanotechnology, selenium nanoparticles have been widely developed to reveal great potential in anticancer, antibacterial, and anti-inflammation treatments. More interestingly, increasing evidence has also shown that functional selenium nanoparticles can be applied for potential immunotherapy, which would achieve more effective treatment efficiency as adjunctive therapy strategies for the current chemotherapy. By directly interacting with innate immune cells, such as macrophages, dendritic cells, and natural killer cells, selenium nanoparticles can regulate innate immunity to intervene disease developments, which were reported to boost the anticancer, anti-infection, and anti-inflammation treatments. Moreover, selenium nanoparticles can also activate and recover different T cells for adaptive immunity regulations to enhance their cytotoxic to combat cancer cells, indicating the potential of selenium nanoparticles for potential immunotherapy strategy development. Here, aiming to enhance our understanding of the potential immunotherapy strategy development based on Se NPs, this review will summarize the immunological regulation effects of selenium nanoparticles and the application of selenium nanoparticle-based immunotherapy strategies. Furthermore, we will discuss the advancing perspective of selenium nanoparticle-based potential immunotherapy as a kind of novel adjunctive therapy to enhance the efficiency of current chemotherapies and also introduce the current obstacles for the development of selenium nanoparticles for potential immunotherapy strategy development. This work is expected to promote the future research on selenium nanoparticle-assisted immunotherapy and finally benefit the more effective disease treatments against the threatening cancer and infectious and chronic diseases.

[An Overview and Interpretation of Important Clinical Studies 
on Non-small Cell Lung Cancer in 2021].

Though the coronavirus disease is still raging in 2021, clinical research on non-small cell lung cancer (NSCLC) did not stop. However, benefiting from advances in lung cancer treatment modality, NSCLC patients have experienced significant improvements in overall survival and quality of life. Currently, research advances on targeted therapy and immunotherapy have together transformed the status of postoperative adjuvant therapy and established a new standard treatment modality for resectable NSCLC. There are equally important research advances in locally advanced and advanced NSCLC, including new treatment modalities, new therapeutic agents, etc., all of which bringing more options for clinical treatment. These therapies will bring changes to NSCLC and will gradually lead to the chronicity of lung cancer in the foreseeable future. Therefore, this paper reviews important studies that will change clinical practice in NSCLC treatment and noteworthy research advances in 2021.
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A Novel Third-generation EGFR Tyrosine Kinase Inhibitor Abivertinib for EGFR T790M-mutant Non-Small Cell Lung Cancer: a Multicenter Phase I/II Study.

PURPOSE: To establish recommended phase II dose (RP2D) in phase I and evaluate safety and efficacy of abivertinib in patients with EGFR Thr790Met point mutation (T790M)-positive(+) non-small cell lung cancer (NSCLC) with disease progression from prior EGFR inhibitors in phase II. PATIENTS AND METHODS: This multicenter, open-label study included 367 adult Chinese patients. Abivertinib at doses of 50 mg twice a day to 350 mg twice a day was evaluated in phase I in continual 28-day cycles, and the RP2D of 300 mg twice a day was used in phase II in continual 21-day cycles. Primary endpoints include RP2D in phase I and objective response rate (ORR) at RP2D in phase II. RESULTS: The RP2D of 300 mg twice a day for abivertinib was established based on pharmacokinetics, efficacy, and safety profiles across doses in phase I. In phase II, 227 patients received RP2D for a median treatment duration of 24.6 weeks (0.43-129). Among 209 response-evaluable patients, confirmed ORR was 52.2% [109/209; 95% confidence interval (CI): 45.2-59.1]. Disease control rate (DCR) was 88.0% (184/209; 95% CI: 82.9-92.1). The median duration of response (DoR) and progression-free survival (PFS) was 8.5 months (95% CI: 6.1-9.2) and 7.5 months (95% CI: 6.0-8.8), respectively. The median overall survival (OS) was 24.9 months [95% CI: 22.4-not reachable (NR)]. All (227/227) patients reported at least 1 adverse event (AE), with 96.9% (220/227) of treatment-related AEs. Treatment-related serious AEs were reported in 13.7% (31/227) of patients. Death was reported in 4.4% (10/227) of patients, and none was deemed as treatment-related. CONCLUSIONS: Abivertinib of 300 mg twice a day demonstrated favorable clinical efficacy with manageable side effects in patients with EGFR T790M+ NSCLC.

High-throughput sequencing-based microsatellite genotyping for polyploids to resolve allele dosage uncertainty and improve analyses of genetic diversity, structure and differentiation: A case study of the hexaploid Camellia oleifera.

Conventional microsatellite (simple sequence repeat, SSR) genotyping methods cannot accurately identify polyploid genotypes leading to allele dosage uncertainty, introducing biases in population genetic analysis. Here, a new SSR genotyping method was developed to directly infer accurate polyploid genotypes. The frequency distribution of SSR sequences was obtained based on deep-coverage high-throughput sequencing data. Corrections were performed accounting for the "stutter peak" and amplification efficiency of SSR sequences. Perl scripts and an online SSR genotyping tool "SSRSeq" were provided to process the sequencing data and output genotypes with corrected allele dosages. Hexaploid Camellia oleifera is the dominant woody oilseed crop in China. Understanding the geographical pattern of genetic variation in wild C. oleifera is essential for the conservation and utilization of genetic resources. Six wild C. oleifera populations were sampled across geographical ranges in subtropical evergreen broadleaf forests of China. Using 35 SSR markers, the high-throughput sequencing-based SSRSeq method was applied to obtain accurate hexaploid genotypes of wild C. oleifera. The results demonstrated that the new method could resolve allele dosage uncertainty and considerably improve genetic diversity, structure and differentiation analyses for polyploids. The genetic variation patterns of wild C. oleifera across geographical ranges agree with the "central-marginal hypothesis", stating that genetic diversity is high in the central population and declines from the central to the peripheral populations, and genetic differentiation increases from the centre to the periphery. This method and findings can facilitate the utilization of wild C. oleifera genetic resources for the breeding of cultivated C. oleifera.

[Efficacy and safety of black tomato concentrate in the treatment of erectile dysfunction: A prospective randomized controlled open trial].

OBJECTIVE: To evaluate the efficacy and safety of black tomato concentrate (BTC), which is rich in polyphenols, in the treatment of ED. METHODS: We conducted a prospective randomized open clinical study of 150 ED patients from December 2018 to February 2020, and treated the them with placebo (n = 50), BTC (n = 50) and Compound Xuanju Capsules (CXC) (n = 50), respectively, all for 8 weeks. Before and at 4 and 8 weeks after treatment, we obtained the scores of the patients on IIEF-5, Erection Hardness Score (EHS), Sexual Encounter Profile (SEP-2,3) and General Assessment Questionnaire (GAQ-1,2), related biochemical indexes and the T level, followed by comparison among the three groups. RESULTS: Totally, 120 of the patients completed the clinical trial, 37 in the placebo, 43 in the BTC and 40 in the CXC group. There were no statistically significant differences among the placebo, BTC and CXC groups in the baseline scores on IIEF-5 (12.03 �� 3.50 vs 11.70 �� 3.80 vs 11.42 �� 3.82), EHS, and SEP-2,3 (P > 0.05). At 8 weeks after treatment, the patients in the BTC group showed significant improvement in IIEF-5 (15.67 �� 3.63), EHS, SEP-2,3 and GAQ-1 positive response compared with those in the placebo group (P < 0.05) and similar improvement to that in the CXC group in IIEF-5 (15.67 �� 3.63 vs 15.65 �� 3.87), EHS, SEP-2,3 and GAQ-1,2 (P > 0.05). No statistically significant differences were observed in the incidence of adverse reactions among the placebo, BTC and CXC groups (4.7% vs 2.7% vs 5.0%, P > 0.05), and the symptoms were significantly relieved in the BTC group after change of the administration time to after meal. CONCLUSION: Black tomato concentrate is comparable to Compound Xuanju Capsules and better than placebo (P < 0.05) in improving the IIEF-5, EHS and SEP-2,3 scores of ED patients. And, with a high safety, it can be used as an alternative treatment of ED.

Successful management of tubular colonic duplication using a laparoscopic approach: A case report and review of the literature.

BACKGROUND: Alimentary duplication is a rare congenital disease with a reported incidence of 1 per 4500 persons, although the exact incidence has been difficult to ascertain. According to previous reports, the most common site of duplication is the ileum, and colonic duplication is rare. Due to different types and locations of the duplication, the manifestations are varied, which makes establishing an accurate diagnosis before surgery a challenge. CASE SUMMARY: A 17-year-old female patient sought evaluation in our department with constipation and chronic abdominal pain for 12 years; she had difficulty defecating and had dry stools since she was a child. An abdominal computed tomography revealed two extremely enlarged loops of bowel full of stool-like intestinal contents in the left lower abdomen, which led us to consider the possibility of colonic duplication. A laparoscopic exploration was performed, which revealed a tubular duplicated colon that shared a common opening with the transverse colon. A left hemi-colectomy was performed with a side-to-side anastomosis. The pathologic results confirmed the diagnosis. At the 6-mo follow-up, the patient was doing well without constipation or abdominal pain. CONCLUSION: Colonic duplication is a rare alimentary abnormality in adults. Due to the non-specific manifestations and low incidence, it is usually difficult to make an accurate diagnosis pre-operatively. Surgery is the mainstay of treatment, even though some patients are asymptomatic.

Circular RNA hsa_circ_0001380 in peripheral blood as a potential diagnostic biomarker for active pulmonary tuberculosis.

Numerous studies have suggested that circular RNAs (circRNAs), a type of non­coding RNA lacking 5'­caps and 3'­poly(A) tails, are involved in the biological processes of various human diseases. However, little is known about their functions and diagnostic value in active pulmonary tuberculosis (APTB). The aim of the present study was to examine whether hsa_circ_0001380 is able to serve as a diagnostic biomarker for patients with APTB. The expression level of hsa_circ_0001380 was detected in the peripheral blood of 32 patients with APTB and 31 healthy volunteers by reverse transcription­quantitative PCR. The functional prediction of hsa_circ_0001380 was performed in silico. RNase R was used to detect the stability of hsa_circ_0001380. Finally, the diagnostic value of hsa_circ_0001380 was evaluated by receiver operating characteristic (ROC) curve analysis. The results showed that hsa_circ_0001380 was significantly downregulated in the peripheral blood of patients with APTB. In addition, hsa_circ_0001380 was found to be resistant to RNase R treatment. Moreover, four N6­adenosine methylation modification sites and two potential microRNA binding sites were predicted in silico. Importantly, the area under the ROC curve was 0.9502, which suggested that hsa_circ_0001380 may act as a diagnostic biomarker for APTB. Taken together, the results indicated that circRNA hsa_circ_0001380 was downregulated in the peripheral blood of patients with APTB, and could serve as a diagnostic biomarker.

Collagen-tussah silk fibroin hybrid scaffolds loaded with bone mesenchymal stem cells promote skin wound repair in rats.

This study demonstrates the efficacy of collagen/tussah silk fibroin (Col/TSF) hybrid scaffolds loaded with bone mesenchymal stem cells (BMSCs) in skin repair. Collagen (Col) and tussah silk fibroin (TSF) were extracted from bovine tendons and tussah cocoons, respectively. Col/TSF scaffolds were obtained using a freeze-drying method and were characterised using fourier transform infrared spectroscopy, scanning electron microscopy, porosity, water retention, thermal stability, and biocompatibility. The results revealed that addition of TSF to scaffolds could enhance their moisturising ability and cell infiltration. The antibacterial properties of Col/TSF scaffolds loaded with antibiotics were also excellent. BMSCs cultured in contact with developed Col/TSF scaffolds showed increased cell adhesion, viability, and differentiation. An in vivo study on rats showed that the Col/TSF scaffold seeded with BMSCs was more conducive to wound healing compared to the Col/TSF scaffold alone. The present study suggests that Col/TSF scaffold seeded with BMSCs could be a promising candidate for skin tissue engineering, due to its excellent skin affinity, good air and water permeability, and improved wound healing potential.

Downregulation of hsa-microRNA-204-5p and identification of its potential regulatory network in non-small cell lung cancer: RT-qPCR, bioinformatic- and meta-analyses.

BACKGROUND: Pulmonary malignant neoplasms have a high worldwide morbidity and mortality, so the study of these malignancies using microRNAs (miRNAs) has attracted great interest and enthusiasm. The aim of this study was to determine the clinical effect of hsa-microRNA-204-5p (miR-204-5p) and its underlying molecular mechanisms in non-small cell lung cancer (NSCLC). METHODS: Expression of miR-204-5p was investigated by real-time quantitative PCR (RT-qPCR). After data mining from public online repositories, several integrative assessment methods, including receiver operating characteristic (ROC) curves, hazard ratios (HR) with 95% confidence intervals (95% CI), and comprehensive meta-analyses, were conducted to explore the expression and clinical utility of miR-204-5p. The potential objects regulated and controlled by miR-204-5p in the course of NSCLC were identified by estimated target prediction and analysis. The regulatory network of miR-204-5p, with its target genes and transcription factors (TFs), was structured from database evidence and literature references. RESULTS: The expression of miR-204-5p was downregulated in NSCLC, and the downtrend was related to gender, histological type, vascular invasion, tumor size, clinicopathologic grade and lymph node metastasis (P<0.05). MiR-204-5p was useful in prognosis, but was deemed unsuitable at present as an auxiliary diagnostic or prognostic risk factor for NSCLC due to the lack of statistical significance in meta-analyses and absence of large-scale investigations. Gene enrichment and annotation analyses identified miR-204-5p candidate targets that took part in various genetic activities and biological functions. The predicted TFs, like MAX, MYC, and RUNX1, interfered in regulatory networks involving miR-204-5p and its predicted hub genes, though a modulatory loop or axis of the miRNA-TF-gene that was out of range with shortage in database prediction, experimental proof and literature confirmation. CONCLUSIONS: The frequently observed decrease in miR-204-5p was helpful for NSCLC diagnosis. The estimated target genes and TFs contributed to the anti-oncogene effects of miR-204-5p.

Low-dose tubacin promotes BMSCs proliferation and morphological changes through the ERK pathway.

Histone deacetylase 6 (HDAC6) plays critical roles in many cellular processes related to cancer, but its epigenetic regulation in bone marrow stromal stem cells (BMSCs) remains unexplored. This study investigated the beneficial effects of Tubulin Acetylation Inducer (tubacin), a novel specific HDAC6 inhibitor, on the proliferation and migration of BMSCs. A low concentration of tubacin promoted BMSC commitment and enhanced proliferation of BMSCs. Atomic force microscopy results showed that tubacin induced morphological changes and enhanced the mechanical properties of BMSCs. Furthermore, low tubacin concentrations significantly upregulated protein expression of acetylated α-tubulin, VCAM-1, and ICAM-1, which could be suppressed by an ERK inhibitor. Protein chip analysis showed that there were significant changes in the expression levels of 49 cytokines after tubacin treatment, which participate in inflammatory responses and cell activation, proliferation, and differentiation. Our findings suggest that the protective effects of tubacin on BMSCs involve HDAC6 inhibition by activating the ERK pathway.

Analysis of resistance mechanisms to abivertinib, a third-generation EGFR tyrosine kinase inhibitor, in patients with EGFR T790M-positive non-small cell lung cancer from a phase I trial.

BACKGROUND: Resistance to third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) presents a major clinical challenge in advanced non-small cell lung cancer (NSCLC). Here, we report resistance mechanisms to abivertinib, a novel third-generation EGFR TKI, from a phase I dose-escalation/expansion study (NCT02330367). METHODS: Patients with EGFR T790M-positive advanced NSCLC and progression on prior EGFR TKIs received abivertinib in dose escalation (50-350 mg twice daily [BID]) or expansion (300 mg BID) cohorts. Patients enrolled at Guangdong Lung Cancer Institute who underwent next-generation sequencing (NGS)-based genomic profiling upon abivertinib progression (prior to October 30, 2018) were enrolled in this exploratory analysis. FINDINGS: Thirty of 73 patients enrolled were eligible for resistance analysis. Upon abivertinib progression, 27 patients provided plasma samples (six patients also provided paired samples from the progression sites) and three patients only provided tissue samples from the progression sites for NGS. A heterogeneous landscape of resistance to abivertinib was observed: 15% (4/27) experienced EGFR T790M loss and 13% (4/30) developing EGFR tertiary mutations including C797S. EGFR amplification was observed in 11 patients (37%), and considered a putative resistance mechanism in seven (23%) patients. Other EGFR-independent resistance mechanisms involved CDKN2A, MET, PIK3CA, HER2, TP53, Rb1 and small-cell lung cancer transformation. INTERPRETATION: Our findings reveal a heterogenous pattern of resistance mechanisms to abivertinib which is distinct from that previously reported with osimertinib. EGFR amplification was the most common resistance mechanism in this cohort. FUND: The National Key R&D Program of China (Grant No. 2016YFC1303800), Key Lab System Project of Guangdong Science and Technology Department - Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2012A061400006/2017B030314120).