Aptamer responsive DNA Functionalized hydrogels electrochemiluminescence biosensor for the detection of adenosine triphosphate.

DNA hydrogel represents a noteworthy biomaterial. The preparation of biosensors by combining DNA hydrogel with electrochemiluminescence can simplify the modification process and raise the experimental efficiency. In this study, an electrochemiluminescence (ECL) biosensor based on DNA hydrogel was fabricated to detect adenosine triphosphate (ATP) simply and quickly. CdTe-Ru@SiO2 nanospheres capable of ECL resonance energy transfer (RET) were synthesized and encapsulated CdTe-Ru@SiO2 in the DNA hydrogel to provide strong and stable ECL signals. DNA hydrogel avoided the labeling of ECL signal molecules. The aptamer of ATP as the linker of the hydrogel for the specificity of ATP detection. The cross-linked structure of the aptamer and the polymer chains was opened by ATP, and then the decomposition of the DNA hydrogel initiated the escape of CdTe-Ru@SiO2 to generate an ECL signal. The designed biosensor detected ATP without too much modification and complex experimental steps on the electrode surface, with good specificity and stability, and a wide linear range. The detection range was 10-5000 nM, and the detection limit was 6.68 nM (S/N = 3). The combination of DNA hydrogel and ECL biosensor provided a new way for clinical detection of ATP and other biomolecule.

Viaminate Inhibits Propionibacterium Acnes-induced Abnormal Proliferation and Keratinization of HaCat Cells by Regulating the S100A8/S100A9- MAPK Cascade.

BACKGROUND: Viaminate, a vitamin A acid drug developed in China, has been clinically used in acne treatment to regulate epithelial cell differentiation and proliferation, inhibit keratinization, reduce sebum secretion, and control immunological and anti-inflammatory actions; however, the exact method by which it works is unknown. METHODS: In the present study, acne was induced in the ears of rats using Propionibacterium acnes combined with sebum application. RESULTS: After 30 days of treatment with viaminate, the symptoms of epidermal thickening and keratin overproduction in the ears of rats were significantly improved. Transcriptomic analysis of rat skin tissues suggested that viaminate significantly regulated the biological pathways of cellular keratinization. Gene differential analysis revealed that the S100A8 and S100A9 genes were significantly downregulated after viaminate treatment. The results of qPCR and Western blotting confirmed that viaminate inhibited the expression of S100A8 and S100A9 genes and proteins in rat and HaCat cell acne models, while its downstream pathway MAPK (MAPK p38/JNK/ERK1/2) protein expression levels were suppressed. Additional administration of the S100A8 and S100A9 complex protein significantly reversed the inhibitory effect of viaminate on abnormal proliferation and keratinization levels in acne cell models. CONCLUSION: In summary, viaminate can improve acne by modulating S100A8 and S100A9 to inhibit MAPK pathway activation and inhibit keratinocyte proliferation and keratinization levels.

Robot versus video-assisted thoracoscopic thymectomy for large thymic epithelial tumors: a propensity-matched analysis.

BACKGROUND: Both video-assisted thoracoscopic surgery (VATS) thymectomy and robot-assisted thoracoscopic surgery (RATS) thymectomy have been suggested as technically sound approaches for early-stage thymic epithelial tumors. However, the choice of VATS or RATS thymectomy for large and advanced thymic epithelial tumors remains controversial. In this study, the perioperative outcomes of VATS and RATS thymectomy were compared in patients with large thymic epithelial tumors (size ≥5.0 cm). METHODS: A total of 113 patients with large thymic epithelial tumors who underwent minimally invasive surgery were included. Sixty-three patients underwent RATS, and 50 patients underwent VATS. Patient characteristics and perioperative variables were compared. RESULTS: Compared with the VATS group, the RATS group experienced a shorter operation time (median: 110 min vs.130 min; P < 0.001) and less blood loss (30.00 ml vs. 100.00 ml, P < 0.001). No patients in the RATS group needed conversion to open surgery, but in the VATS series, five patients required conversion to open procedures (0% vs. 14.29%, P = 0.054). The rate of concomitant resection in the RATS group was similar to that in the VATS group (11.43% vs. 5.71%; P = 0.673). There was no significant difference between the two groups in the duration of chest tube (P = 0.587), postoperative complications (P = 1.000), and the duration of postoperative hospital stay (P = 0.141). CONCLUSION: For large thymic epithelial tumors, RATS thymectomy can be performed safely and effectively in a radical fashion. Due to the advanced optics and precise instrument control, concomitant resections can be easily achieved in larger thymic epithelial tumors using the robotic approach.

Effect of initiative pulmonary bullectomy on the risk of post-operative pneumothorax in patients with esophageal carcinoma: a propensity score-matched analysis.

Background: Postoperative pneumothorax can lead to additional invasive intervention and extended hospitalization. The effect of initiative pulmonary bullectomy (IPB) during the esophagectomy on preventing postoperative pneumothorax remains controversial. This study evaluated the efficacy and safety of IPB in patients who underwent minimally invasive esophagectomy (MIE) for esophageal carcinoma complicated by ipsilateral pulmonary bullae. Methods: Data from 654 consecutive patients with esophageal carcinoma who underwent MIE from January 2013 to May 2020 were retrospectively collected. A total of 109 patients who had a definite diagnosis of ipsilateral pulmonary bullae were recruited and classified into two groups: the IPB group and the control group (CG). Propensity score matching (PSM, match ratio =1:1), incorporating preoperative clinical features, was used to compare the perioperative complications and analyze efficacy and safety between IPB and control group. Results: The incidences of postoperative pneumothorax in the IPB and control groups was 3.13% and 40.63% respectively, with a significant difference (P<0.001). Logistic analyses indicated that removing ipsilateral bullae was associated with a lower risk (OR 0.030; 95% CI: 0.003-0.338; P=0.005) of incident postoperative pneumothorax. No significant difference was found between the two groups in terms of the incidence of anastomotic leakage (6.25% vs. 3.13%, P=1.000), arrhythmia (3.13% vs. 3.13%, P=1.000), chylothorax (0% vs. 3.13%, P=1.000) and other common complications. Conclusions: In esophageal cancer patients with ipsilateral pulmonary bullae, IPB performed in the same anesthesia process is an effective and safe method for the prevention of postoperative pneumothorax, allowing for a shorter postoperative rehabilitation time, and it does not exert unfavorable effects on complications.

Robot-assisted thymectomy in large anterior mediastinal tumors: A comparative study with video-assisted thymectomy and open surgery.

BACKGROUND: The aim of this study was to evaluate the safety and effectiveness of robot-assisted thymectomy (RAT) in large anterior mediastinal tumors (AMTs) (size ≥6 cm) compared with video-assisted thymectomy (VAT) and open surgery. METHODS: A total of 132 patients with large AMTs who underwent surgical resection from January 2016 to June 2022 were included in this study. A total of 61 patients underwent RAT, 36 patients underwent VAT and 35 patients underwent open surgery. Perioperative outcomes were compared. RESULTS: There were no significant differences in tumor size (p = 0.141), or pathological types (p = 0.903). Compared with the open group, the RAT and VAT groups were associated with a shorter operation time (115.00 vs. 160.00, p = 0.012; 122.50 vs. 160.00, p = 0.071), and less blood loss (50.00 vs. 200.00, p < 0.001; 50.00 vs. 200.00, p < 0.001), respectively. The rate of conversion in the RAT group was similar to that in the VAT group (6.56% vs. 13.89%, p = 0.229). Concomitant resection was less frequently performed in the VAT group than in the RAT and open groups (5.56% vs. 31.15%, p = 0.040; 5.56% vs. 31.43%, p = 0.006). VAT patients had a lower drainage volume (365.00 vs. 700.00 and 910.00 mL, p < 0.001), shorter duration of chest tube (2.00 vs. 3.00 and 4.00, p < 0.001), and shorter hospital stay (5.00 vs. 6.00 and 7.00, p < 0.001) than the RAT and open groups. There was no 30-day mortality in any group. No difference was seen in R0 resection rates (p = 0.846). The postoperative complication rates were similar among the three groups (p = 0.309). Total in-hospital costs (66493.90 vs. 33581.05 and 42876.40, p < 0.001) were significantly higher in the RAT group. CONCLUSIONS: RAT is safe and effective for the resection of large AMTs compared to VAT and open surgery. Vascular resection in RAT is technically feasible. A long-term follow-up is required.

Manipulating Metabolic Alterations and their Consequences to Unleash the Potential of Antitumor Immunotherapy.

Cellular metabolic reprogramming driven by oncogenic mutations is considered as a hallmark in the development of malignant cells, and has been a focus over the past decade. A common theme emerging from these metabolic alterations is that tumor cells can acquire necessary nutrients from a nutrient-limited microenvironment and utilize them to sustain growth and unrestrained cellular division. However, this significant metabolic flexibility and the hostile microenvironment caused by the insufficient vascular exchange, depletion of nutrients, hypoxia, and accumulation of waste products, can inhibit the metabolism and immune activity of tumor-infiltrating lymphocytes and impose barriers to effective antitumor immunotherapies. In this perspective, we review the classical alterations in tumorigenesis- associated metabolic reprogramming and examine the functional contribution of these aberrant metabolisms to the establishment and maintenance of an immunosuppressive microenvironment. Furthermore, we explore the possible approaches to targeting on these metabolic pathways to achieve antitumor immunotherapy, as well as some hypothetical or ongoing combination therapeutic strategies that could, to a certain extent, biologically rationalize and broaden the utility of immune checkpoint inhibitors. Ultimately, we elucidate some dietary modifications that can limit tumor-specific nutritional requirements and maximize the cytotoxicity of other antineoplastic drugs.

Effects of Glucose Metabolism, Lipid Metabolism, and Glutamine Metabolism on Tumor Microenvironment and Clinical Implications.

In recent years, an increasingly more in depth understanding of tumor metabolism in tumorigenesis, tumor growth, metastasis, and prognosis has been achieved. The broad heterogeneity in tumor tissue is the critical factor affecting the outcome of tumor treatment. Metabolic heterogeneity is not only found in tumor cells but also in their surrounding immune and stromal cells; for example, many suppressor cells, such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and tumor-associated T-lymphocytes. Abnormalities in metabolism often lead to short survival or resistance to antitumor therapy, e.g., chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Using the metabolic characteristics of the tumor microenvironment to identify and treat cancer has become a great research hotspot. This review systematically addresses the impacts of metabolism on tumor cells and effector cells and represents recent research advances of metabolic effects on other cells in the tumor microenvironment. Finally, we introduce some applications of metabolic features in clinical oncology.

Effectiveness and safety of Adalimumab in psoriasis and its influence on gut microbiome.

Psoriasis is an inflammatory immune-mediated skin disease that significantly impacts physical and psychological well-being. Adalimumab (ADA), a tumor necrosis factor (TNF)-α antagonist, is used to treat psoriasis. This study was performed to assess the efficacy and safety of ADA, identify the fecal microbial composition of psoriasis patients, and explore the effect of ADA on the gut bacteria in psoriasis. Clinical characteristics of the 13 psoriasis patients before (BT) and after ADA treatment (AT) were collected. And total 39 fecal samples from 13 psoriasis patients (BT and AT) and 13 healthy controls were sequenced by 16S rRNA and analyzed by informatics methods. After three months' ADA treatment, physician global assessment (PGA), psoriasis area and severity index (PASI), dermatology life quality index (DLQI), state-trait anxiety inventory (STAI), and itch numeric rating scale (NRS) scores all decreased, and there were no severe adverse effects. Besides, the microbiota of the psoriasis group differed from that of the healthy group, but no microbial diversity and composition alteration were observed between psoriasis patients BT and AT. We suggested that the gut microbiome may change more slowly than skin lesions. Long-term follow-up of patients treated with ADA and further study of psoriasis based on microbiota may provide more evidence for the treatment of psoriasis.

MPMR: Multi-Scale Feature and Probability Map for Melanoma Recognition.

Malignant melanoma (MM) recognition in whole-slide images (WSIs) is challenging due to the huge image size of billions of pixels and complex visual characteristics. We propose a novel automatic melanoma recognition method based on the multi-scale features and probability map, named MPMR. First, we introduce the idea of breaking up the WSI into patches to overcome the difficult-to-calculate problem of WSIs with huge sizes. Second, to obtain and visualize the recognition result of MM tissues in WSIs, a probability mapping method is proposed to generate the mask based on predicted categories, confidence probabilities, and location information of patches. Third, considering that the pathological features related to melanoma are at different scales, such as tissue, cell, and nucleus, and to enhance the representation of multi-scale features is important for melanoma recognition, we construct a multi-scale feature fusion architecture by additional branch paths and shortcut connections, which extracts the enriched lesion features from low-level features containing more detail information and high-level features containing more semantic information. Fourth, to improve the extraction feature of the irregular-shaped lesion and focus on essential features, we reconstructed the residual blocks by a deformable convolution and channel attention mechanism, which further reduces information redundancy and noisy features. The experimental results demonstrate that the proposed method outperforms the compared algorithms, and it has a potential for practical applications in clinical diagnosis.

Baicalein protects human vitiligo melanocytes from oxidative stress through activation of NF-E2-related factor2 (Nrf2) signaling pathway.

Vitiligo is a complex disorder characterized by patchy loss of skin pigmentation due to abnormal melanocyte function. Overwhelming evidences have suggested that oxidative stress plays a major role in the loss of melanocytes thereby mediating the onset and progression of vitiligo. The nuclear factor erythroid 2-like factor 2 (Nrf2) is a master regulator of cellular redox homeostasis and the activation of Nrf2 signaling pathway is impaired in the vitiligo melanocytes. Baicalein, as flavonoid extracted from the Scutellaria baicalensis, has been proved to possess the ability to activate Nrf2 signaling pathway in other cell types and mouse model. Our previous data found that baicalein exerts a cytoprotective role in H2O2-induced apoptosis in human melanocytes cell line (PIG1). Based on these founding, we hypothesized that baicalein activates Nrf2 signaling pathway, alleviates H2O2-induced mitochondrial dysfunction and cellular damage, thereby protecting human vitiligo melanocytes from oxidative stress. In the present study, we found that baicalein effectively inhibited H2O2-induced cytotoxicity and apoptosis in human vitiligo melanocytes (PIG3V). Further results demonstrated that baicalein promoted Nrf2 nucleus translocation as well as up-regulated the expression of Nrf2 and its target gene, heme oxygenase-1 (HO-1). Moreover, the protective effects of baicalein against H2O2-induced cellular damage and apoptosis as well as mitochondrial dysfunction were abolished by Nrf2 knockdown. Additionally, we observed that Nrf2 knockdown suppressed proliferation and increased the sensitivity of PIG3V cells to H2O2 treatment. Finally, we explored the mechanism of baicalein associated with Nrf2 activation and found that the phosphorylation of Nrf2 as well as ERK1/2and PI3K/AKT signaling were not involved in the baicalein-induced activation of Nrf2. Taken together, these data clearly suggest that baicalein enhances cellular antioxidant defense capacity of human vitiligo melanocytes through the activation of the Nrf2 signaling pathway, providing beneficial evidence for the application of baicalein in the vitiligo treatment.

The revision of 8th edition TNM stage criteria is more accurate in prediction postoperative survival for SCLC patients.

OBJECTIVES: The 8th edition TNM lung cancer classification was enacted in January 2017. An important change is the old T2a was revised to new T2a and T2b. Whether a postoperative survival difference exists between the two stages is still undefined. The purpose of this study is to investigate the postoperative outcomes of small cell lung cancer (SCLC) patients and compare the survival difference between the two stages. METHODS: Data of patients with SCLC who underwent surgery between October 2005 and August 2013 at our institute were reviewed. A total number of 194 patients were enrolled and were reclassified according to the 8th edition TNM stage. Survival was determined by Kaplan-Meier analysis, the log-rank test was used to compare survival differences. RESULTS: Surgical resection included 165 lobectomy or bilobectomy, 19 sublobectomy and 10 pneumonectomy. There were 159 patients received chemotherapy, 35 underwent surgery alone. The 5-year survival rate and median survival time (MST) of whole group was 34.5% and 45 months. For patients who received similar therapy (surgery plus chemotherapy) in N0 stage, the MST of T2a stage was 83 months, significantly longer than 62 months in T2b stage (P = 0.017). CONCLUSIONS: In the 8th edition TNM lung cancer stage criteria, the postoperative survival of T2a is superior to T2b for non-metastatic SCLC at N0 stage.

Pulmonary inflammatory myofibroblastic tumor versus IgG4-related inflammatory pseudotumor: differential diagnosis based on a case series.

BACKGROUND: Pulmonary inflammatory myofibroblastic tumor (IMT) has been considered as a synonym for inflammatory pseudotumor (IPT) for a long time. Recent studies have indicated that IMT and IgG4-related IPT are distinct diseases. However, no consensus criteria have been recommended. Here we propose a set of criteria for the differential diagnosis. METHODS: Twenty-six archived IMT and IgG4-related IPT samples were examined for histological characteristics and the expression of IgG, IgG4, SMA and ALK-1. Based on our proposed criteria, we reclassified the cases into either IMT or IgG4-related IPT group and compared the clinicopathological features, laboratory findings, overall survivals (OS) and disease-free survivals between groups to validate the effectiveness and dependability of the diagnostic criteria. RESULTS: The average age of IgG4-related IPT group was higher than IMTs (48.82 vs. 39.22 years, P=0.031). In IMT group, tumors were characterized by bigger tumor sizes (3.47 vs. 2.22 cm, P=0.007), diffuse and total destroyed alveoli (88.89% vs. 17.65%, P=0.002), fewer lymphoid follicles (1.6/HPF vs. 3.0/HPF, P=0.045) and lower expression of IgG (74.7/HPF vs. 149.1/HPF; P<0.001). As an exclusion criterion of IgG4-related IPT, ALK-positivity was correlated with the higher cytological atypia (mean 3.7/HPF, P<0.001) and lesser lymphoid follicles (mean 1.2/HPF, P=0.021). And it's the first study to show the liner positive correlation between the lymphocytes + plasma cells count and IgG4-positive plasma cells count in these lesions (r=0.914, P<0.001). The negative correlation between the IgG4-positive plasma cells count and the expression of ALK-1 are reported for the first time as well (rs=-0.632, P=0.001). However, despite two patients with recurrence or metastasis were divided into IMT group, only borderline values were detected in the survival analysis (OS 88.89% vs. 100%, P=0.197, DFS 77.78% vs. 100.00%; P=0.056). CONCLUSIONS: The significant differences of clinicopathological characteristics between the IMTs and IgG4-related IPTs indicated that a combination of lymphocytes + plasma cells count, cytological atypia, IgG4 and ALK-1 staining will be helpful in differential diagnosis.

[Long term outcomes of patients with stage I lung cancer treated by single-direction video-assisted thoracoscopic surgery lobectomy or segmentectomy].

OBJECTIVE: To observe the outcome of stage I lung cancer treated by single-direction video-assisted thoracoscopic surgery (SD-VATS) major lung resection. METHODS: Between May 2006 and December 2013, a total of 3 743 patients with lung cancer underwent surgical treatment in Department of Thoracic Surgery, West China Hospital. The clinical date of 783 patients with stage I lung cancer treated by SD-VATS lobectomy/segmentectomy was analyzed retrospectively. There were 388 males and 395 females with a mean age of (59 ± 10) years (range 25 to 86 years). There were 740 cases of lobectomy and 43 cases of segmentectomy. Twenty patients underwent conversion to open thoracotomy. The methods of Kaplan-Meier survival analysis and Cox proportional hazard regression model were used to investigate the long term outcome and prognostic factors. RESULTS: The mean operating time was (145 ± 54) minutes (range 70 to 460 minutes). The median intraoperative blood loss was 50 (70) ml (range 5 to 1 200 ml). The postoperative morbidity and 90-day mortality were 13.3% and 1.0%, respectively. 5.9% patients were lost to follow-up. Finally 730 patients were enrolled into prognostic analysis with a mean follow-up time of (37 ± 18) months (range 5 to 92 months). The 5-year overall survival (OS), disease free survival (DFS), and cancer specific survival (CSS) were 83.8%, 74.4%, and 86.6%, respectively. The 5-year OS of IA and IB were 90.7% and 79.8% respectively. Univariate and multivariate analysis indicated that age ≥ 60 years (OR = 1.786, 95% CI: 1.081 to 2.948, P = 0.023), non-adenocarcinoma (OR = 1.647, 95% CI: 1.204 to 2.253, P = 0.002), and higher T status (OR = 2.709, 95% CI: 1.031 to 7.121, P = 0.043) were independently associated with poor OS; higher T status (OR = 5.118, 95% CI: 2.330 to 11.240, P = 0.000) and higher pathological stage status (OR = 0.369, 95% CI: 0.137 to 0.991, P = 0.048) were independently associated with poor DFS; non-adenocarcinoma (OR = 1.717, 95% CI: 1.224 to 2.409, P = 0.002) and higher T status (OR = 5.029, 95% CI: 1.432 to 17.659, P = 0.012) were independently associated with poor CSS. CONCLUSION: SD-VATS lung cancer resection is a safe and feasible method for the treatment of stage I lung cancer resulting good outcomes.