Publications by authors named "Long Jiang"

528 Publications

Screening for lung cancer in individuals who never smoked: An IASLC Early Detection and Screening Committee Report.

J Thorac Oncol 2021 Aug 26. Epub 2021 Aug 26.

Division of Respiratory Medicine and Thoracic Oncology, Department of Internal Medicine V, Thoracic Oncology Centre Munich, University of Munich - Campus Innenstadt, Munich, Germany.

Screening with Low-dose computed tomography (LDCT) of high-risk individuals with a smoking history reduces lung cancer mortality. Current screening guidelines and eligibility criteria can miss over 50% of lung cancers, and in some geographical areas, like East Asia, a large proportion of the missed lung cancers are in never-smokers. Although randomized trials demonstrated the benefits of screening for people who smoke, these trials generally excluded never-smokers. Thus, the feasibility and effectiveness of lung cancer screening of individuals never -smoked is uncertain. Several known and suspected risk factors for lung cancers in never-smokers such as exposure to secondhand smoke, occupational carcinogens, radon, air pollution, and pulmonary diseases, such as COPD and interstitial lung diseases and intrinsic factors, such as age are well noted. In this regard, knowledge of risk factors may make possible quantification and prediction of lung cancer risk in never-smokers. It is worth considering if and how never-smokers could be included in population-based screening programs. As the implementation of these programs is challenging in many countries due to multiple factors and the epidemiological differences by global regions, these issues will need to be evaluated in each country taking into account various factors, including accuracy of risk assessment and cost-effectiveness of screening in never-smokers. This report aims to outline current knowledge about risk factors for lung cancer in never-smokers, to propose research strategies for this topic, and initiate a broader discussion about lung cancer screening of never-smokers. Similar considerations can be made in current and ex-smokers, which don't fulfill the current screening inclusion criteria, but otherwise are at increased risk. Although screening of never-smokers may in the future be effectively conducted, current evidence to support widespread implementation of this practice is lacking.
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http://dx.doi.org/10.1016/j.jtho.2021.07.031DOI Listing
August 2021

Circ_0062270 upregulates EPHA2 to facilitate melanoma progression via sponging miR-331-3p.

J Dermatol Sci 2021 Aug 19. Epub 2021 Aug 19.

Department of Dermatologic Surgery, Shanghai Skin Disease Hospital, Shanghai, China. Electronic address:

Background: Circular RNA (circRNA) has been confirmed to play a vital role in melanoma progression.

Objective: The regulatory function of circ_0062270, a novel circRNA, in melanoma progression is unclear.

Methods: Relative expression levels of circ_0062270 and microRNA (miR)-331-3p were determined using qRT-PCR. Cell counting kit 8 assay, EdU staining and flow cytometry were used to measure cell proliferation, cell cycle distribution and apoptosis. The protein levels of proliferation, apoptosis and metastasis-related markers, as well as EPH receptor A2 (EPHA2), were tested using western blot analysis. Besides, cell migration and invasion were evaluated using transwell assay. Meanwhile, the interaction between miR-331-3p and circ_0062270 or EPHA2 was confirmed by dual-luciferase reporter assay or RIP assay. Additionally, tumor xenograft models were constructed to investigate the function of circ_0062270 on melanoma tumor growth in vivo.

Results: The expression of circ_0062270 was increased in melanoma tissues and cells. Knockdown of circ_0062270 inhibited proliferation, promoted apoptosis, and repressed metastasis in melanoma. Moreover, circ_0062270 could serve as miR-331-3p sponge, and miR-331-3p could target EPHA2. Furthermore, miR-331-3p inhibitor and EPHA2 overexpression reversed the inhibitory effect of circ_0062270 silencing on melanoma progression. In addition, silenced circ_0062270 also could inhibit melanoma tumor growth in vivo.

Conclusion: Circ_0062270 accelerated the progression of melanoma through regulating the miR-331-3p/EPHA2 axis, suggesting that circ_0062270 might be a novel potential therapeutic target for melanoma.
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http://dx.doi.org/10.1016/j.jdermsci.2021.08.005DOI Listing
August 2021

Accurate and Nonpurified Identification of Extracellular Vesicles Using Dual-Binding Recognition Mode.

Anal Chem 2021 09 27;93(36):12383-12390. Epub 2021 Aug 27.

School of Biological Sciences and Technology, University of Jinan, Jinan 250022, P.R. China.

Circulating extracellular vesicles (EVs) are promising biomarkers for the early diagnosis and prognosis of cancer in a non-invasive manner. However, the rapid and accurate identification of EVs in complex biological samples is technically challenging, which is attributed to the requirement of extensive sample purification and unsatisfactory detection accuracy due to the disturbance of interfering proteins. Herein, a simultaneous binding of double-positive EV membrane protein-based recognition mode (DRM) is proposed. By the combination of DRM-mediated toehold activation and G-quadruplex DNAZyme-catalyzed etching of [email protected] nanorods ([email protected] NRs), we have developed an accurate, non-purified, low-cost, and visual strategy for EV identification. The synchronous binding of double-positive proteins on EV membranes is validated by confocal laser scanning microscopy analysis. This approach exhibits excellent specificity and sensitivity toward EVs ranging from 1.0 × 10 to 1.0 × 10 particles/mL with a detection limit of 6.31 × 10 particles/mL. Moreover, we have successfully realized non-purified EV quantification in complex biological media. In addition, target-initiated catalyzed hairpin assembly (CHA) is integrated with G-quadruplex DNAZyme-catalyzed color variation of [email protected] NRs; thus, low-background EV detection can be achieved by the naked eye. Furthermore, our strategy is easy to adapt to high-throughput formats by using an automatic microplate reader, which could be expected to meet the requirements for high-throughput detection of clinical samples. With its capacities of rapidness, portability, affordability, high throughput, non-purification, and visual detection, this strategy could provide a practical tool for accurate identification of EVs and early diagnosis of cancer.
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http://dx.doi.org/10.1021/acs.analchem.1c02259DOI Listing
September 2021

Polymeric Composite Matrix with High Biobased Content as Pharmaceutically Relevant Molecular Encapsulation and Release Platform.

ACS Appl Mater Interfaces 2021 Sep 23;13(34):40229-40248. Epub 2021 Aug 23.

Department of Coatings and Polymeric Materials, North Dakota State University, Fargo, North Dakota 58108, United States.

Drug delivery systems (DDS) that can temporally control the rate and extent of release of therapeutically active molecules find applications in many clinical settings, ranging from infection control to cancer therapy. With an aim to design a locally implantable, controlled-release DDS, we demonstrated the feasibility of using cellulose nanocrystal (CNC)-reinforced poly (l-lactic acid) (PLA) composite beads. The performance of the platform was evaluated using doxorubicin (DOX) as a model drug for applications in triple-negative breast cancer. A facile, nonsolvent-induced phase separation (NIPS) method was adopted to form composite beads. We observed that CNC loading within these beads played a critical role in the mechanical stability, porosity, water uptake, diffusion, release, and pharmacological activity of the drug from the delivery system. When loaded with DOX, composite beads significantly controlled the release of the drug in a pH-dependent pattern. For example, PLA/CNC beads containing 37.5 wt % of CNCs showed a biphasic release of DOX, where 41 and 82% of the loaded drug were released at pH 7.4 and pH 5.5, respectively, over 7 days. Drug release followed Korsmeyer's kinetics, indicating that the release mechanism was mostly diffusion and swelling-controlled. We showed that DOX released from drug-loaded PLA/CNC composite beads locally suppressed the growth and proliferation of triple-negative breast cancer cells, MBA-MB-231, via the apoptotic pathway. The efficacy of the DDS was evaluated in human tissue explants. We envision that such systems will find applications for designing biobased platforms with programmed stability and drug delivery functions.
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http://dx.doi.org/10.1021/acsami.1c03805DOI Listing
September 2021

A risk score for predicting postoperative complications in non-intubated thoracic surgery.

J Thorac Dis 2021 Jul;13(7):3960-3968

Department of Cardiothoracic Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: The risk factors for postoperative complications in non-intubated video-assisted thoracoscopic surgery (VATS) have not been observed before. Here to develop a simple risk score to predict the risk of postoperative complications for patients who scheduling non-intubated VATS, which is beneficial to guide the clinical interventions.

Methods: A total of 1,837 patients who underwent non-intubated VATS were included from January 2011 to December 2018. A development data set and a validation data set were allocated according to an approximate 3:2 ratio of total cases. The stepwise logistic regression was used to establish a risk score model, and the methods of bootstrap and split-sample were used for validation.

Results: Multivariable analysis revealed that the forced expiratory volume in the first second in percent of predicted, the anesthesia method, blood loss, surgical time, and preoperative neutrophil ratio were risk factors for postoperative complications. The risk score was established with these 5 factors, varied from 0 to 53, with the corresponding predicted probability of postoperative complications occurrence ranged from 1% to 92% and was calibrated (Hosmer-Lemeshow χ =6.261; P=0.618). Good discrimination was acquired in the development and validation data sets (C-statistic 0.705 and 0.700). A positive correlation was between the risk score and postoperative complications (P for trend <0.01). Three levels of low-risk (0-15 points], moderate-risk (15-30 points], and high-risk (>30 points] were established based on the score distribution of postoperative complications.

Conclusions: This simple risk score model based on risk factors of postoperative complications can validly identify the high-risk patients with postoperative complications in the non-intubated VATS, and allow for early interventions.
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http://dx.doi.org/10.21037/jtd-21-636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339752PMC
July 2021

Investigation of organic impurity and its occurrence in industrial waste salt produced by physicochemical process.

PLoS One 2021 20;16(8):e0256101. Epub 2021 Aug 20.

Dongjiang Environmental Co., Ltd., Shenzhen, Guangdong, China.

Industrial waste salt is classified as hazardous waste to the environment. The organic impurity and its occurrence in industrial waste salt affect the salt resource utilization. In this paper, composition quantitative analysis, XRD, TG-DSC, SEM/FIB-SEM coupled with EDS, FTIR, XPS and GC-Ms were chosen to investigate the organic impurity and its occurrence in industrial waste salt. The organic impurities owe small proportion (1.77%) in the specimen and exhibit weak thermal stability within the temperature of 600°C. A clear definition of organic impurity, including 11 kinds of organic compounds, including aldehyde, benzene and its derivatives etc., were detected in the industrial waste salt. These organic impurities, owing (C-O/C-O-C, C-OH/C = O, C-C/CHx/C = C etc.)-containing function group substance, are mainly distributed both on the surface and inside of the salt particles. Meanwhile, the organic substance may combine with metal cations (Ni2+, Mg2+, Cu2+ etc.) through functional groups, such as hydroxide, carbonyl etc., which increases its stability in the industrial waste salt. These findings provide comprehensive information for the resource utilization of industrial waste salt from chemical industry etc.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0256101PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378702PMC
August 2021

Silicate bioceramics elicit proliferation and odonto-genic differentiation of human dental pulp cells.

Dent Mater J 2021 Aug 19. Epub 2021 Aug 19.

Department of General Dentistry, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology.

This study aimed to investigate the effects of silicates on the proliferation and odontogenic differentiation of human dental pulp cells (hDPCs) in vitro. HDPCs were cultured in the presence of calcium silicate (CS) extracts, while calcium hydroxide (CH) extracts and culture medium without CH or CS were used as the control groups. The calcium and phosphorus ion concentrations in the CS were similar to those in the control groups, but the concentration of silicon ions in the CS extracts was higher than that in the control groups. HDPCs cultured with CS and CH extracts at dilution of 1/128 proliferated significantly more than those cultured with the control treatments. CS extracts promoted cell migration, enhanced the expression of odontogenic marker genes and conspicuously increased odontogenesis-related protein production and the release of cytokines, suggesting that CS bioactive ceramics possess excellent biocompatibility and bioactivity and have the potential for application as pulp-capping agents.
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http://dx.doi.org/10.4012/dmj.2021-042DOI Listing
August 2021

Preparation of Activated Carbon Doped with Graphene Oxide Porous Materials and Their High Gas Adsorption Performance.

ACS Omega 2021 Aug 22;6(30):19799-19810. Epub 2021 Jul 22.

Key Laboratory of Coal Resources Exploration and Comprehensive Utilization, Ministry of Natural Resources, Xi'an, Shaanxi 710021, China.

It is still a great challenge to develop a new porous carbon adsorbent with excellent separation performance and to recover low-concentration CH in coal mine gas. This work provides a new idea for the study of CH adsorption on activated carbon (AC) composites. Composite materials with microporous structures were prepared from coconut-shell activated carbon (CAC) doped with graphene oxide (GO) by a chemical activation process in this paper. The expansion and dissociation of GO at high temperatures indirectly improve the specific surface area (SSA) of the composite. The interlayer aggregation is reduced, the activation effect is improved, and a new low-cost adsorption material is prepared. The SSA of CAC-50 is more than 3000 m·g. A high SSA and a narrow pore size distribution lead to a higher total adsorption capacity of CH. The breakthrough test also confirmed that AC/GOs had a better adsorption capacity for CH. The separation performance of the CH/N mixture is not good at room temperature, which is due to the influence of a high SSA and average pore size. As a low-cost and rich material, CAC has a wide range of application prospects. The composite is a potential material for recovering low-concentration CH from the coal mine, which is worthy of attention. In the future, the selectivity of AC/GOs to CH can be increased by loading functional groups or modification.
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http://dx.doi.org/10.1021/acsomega.1c02416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340399PMC
August 2021

A three-dimensional dynamic DNA walker-mediated branching hybridization chain reaction for the ultrasensitive fluorescence sensing of ampicillin.

Analyst 2021 Sep 4;146(17):5413-5420. Epub 2021 Aug 4.

School of Water Conservancy and Environment, University of Jinan, Jinan 250022, P.R. China.

In this study, a novel, rapid and ultrasensitive fluorescence strategy using the three-dimensional (3D) dynamic DNA walker (DW)-induced branched hybridization chain reaction (bHCR) has been proposed for the detection of ampicillin (AMP). The sensing system was composed of an Nt·Bbvcl-powered DNA walker blocked by an AMP aptamer, hairpin-shaped DNA track probe (TP) and four kinds of metastable hairpin probes as the substrates of bHCR, which triggered the formation of the split G-quadruplex as the signal molecule. Due to the reasonable design, the specific binding between AMP and its aptamer activated the DW, and the DW moved on the surface of the gold nanoparticles (AuNPs) with the help of Nt·Bbvcl to produce primer probes (PPs), which induced bHCR. The products of the bHCR gathered two split G-quadruplex sequences together to form one complete G-quadruplex. The formed G-quadruplex emitted a strong fluorescence signal in the presence of thioflavin-T (ThT) to achieve the purpose of detecting AMP. The sensitivity of this method was greatly improved by the use of the 3D DNA walker and bHCR. The split G-quadruplex enhanced the signal-to-noise ratio (SNR). Under the optimal experimental conditions, a good correlation was obtained between the fluorescence intensity of the sensing system and the concentration of AMP ranging from 5 pM to 500 nM with a limit of detection (LOD) of 3.68 pM. Simultaneously, the method has been applied to the detection of antibiotics in spiked milk samples with satisfactory results.
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http://dx.doi.org/10.1039/d0an02226hDOI Listing
September 2021

High lipoprotein(a) concentrations are associated with lower type 2 diabetes risk in the Chinese Han population: a large retrospective cohort study.

Lipids Health Dis 2021 Jul 27;20(1):76. Epub 2021 Jul 27.

Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Background: Lipoprotein (a) [Lp(a)] is a proven independent risk factor for coronary heart disease. It is also associated with type 2 diabetes mellitus (T2DM). However, the correlation between Lp(a) and T2DM has not been clearly elucidated.

Methods: This was a retrospective cohort study involving 9248 T2DM patients and 18,496 control individuals (1:2 matched). Patients were randomly selected from among inpatients in the Second Affiliated Hospital of Nanchang University between 2006 and 2017. Clinical characteristics were compared between the two groups. Spearman rank-order correlation coefficients were used to evaluate the strength and direction of monotonic associations of serum Lp(a) with other metabolic risk factors. Binary logistic regression analysis was used to establish the correlation between Lp(a) levels and T2DM risk.

Results: The median Lp(a) concentration was lower in T2DM patients than in controls (16.42 vs. 16.88 mg/dL). Based on four quartiles of Lp(a) levels, there was a decrease in T2DM risk from 33.7% (Q1) to 31.96% (Q4) (P for trend < 0.0001). Then, Lp(a) levels > 28.72 mg/dL (Q4) were associated with a significantly lower T2DM risk in the unadjusted model [0.924 (0.861, 0.992), P = 0.030]. Similar results were obtained in adjusted models 1 [Q4, 0.925 (0.862, 0.993), P = 0.031] and 2 [Q4, 0.919 (0.854, 0.990), P = 0.026]. Furthermore, in the stratified analysis, Q4 of Lp(a) was associated with a significantly lower T2DM risk among men [0.813 (0.734, 0.900), P < 0.001] and those age > 60 years [0.819 (0.737, 0.910), P < 0.001]. In contrast, the low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) did not impact these correlations between Lp(a) and diabetes.

Conclusions: There is an inverse association between Lp(a) levels and T2DM risk in the Chinese population. Male patients, especially those aged more than 60 years with Lp(a) > 28.72 mg/dL, are low-risk T2DM individuals, regardless of LDL-C levels and CHD status.
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http://dx.doi.org/10.1186/s12944-021-01504-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8317300PMC
July 2021

Impact of off-bottom seaweed cultivation on turbulent variation in the hydrodynamic environment: A flume experiment study with mimic and natural Saccharina latissima thalli.

Sci Total Environ 2021 Jul 14;797:149048. Epub 2021 Jul 14.

Department of Estuarine and Delta Systems, NIOZ Netherlands Institute for Sea Research, P.O. Box 140, 4400 AC Yerseke, the Netherlands. Electronic address:

The seaweed industry is growing worldwide to meet future resource needs in terms of food and fuel. In the meantime, the impact of expanding off-bottom seaweed cultivation on its environment is unclear. For example, it remains poorly understood how off-bottom seaweeds affect the local hydrodynamic environment, especially concerning turbulence that is more important for nutrient transport and availability than the mean flow velocity. Here, we carried out well-controlled flume experiments with mimic seaweed thalli, which are available, controllable, and stable, to investigate the impact of off-bottom seaweed canopies on whole-depth flow velocities in terms of both mean flow and turbulence velocity profiles. A careful comparison of behavior in the flow between natural and mimic seaweed thalli was made before these experiments. The results show that the floating seaweed thalli generate a surface boundary layer and have a profound impact on the velocity structure in the bottom boundary layer. More importantly, the generation, growth and dissipation of turbulence in the seaweed thalli area deeply affect the downstream distribution of near-bed turbulent strength and associated bed shear stress. Ignoring this turbulent variation would cause inaccurate predictions of morphological changes of the seabed. Our findings suggest that expanding the seaweed cultivation area may cause high risks of bed degradation and low diffusion in the downstream cultivation area. These findings provide novel insights into the environmental influence of off-bottom seaweed cultivation, with important implications for optimizing management strategies to promote seaweed productivity while minimizing seabed destabilization.
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http://dx.doi.org/10.1016/j.scitotenv.2021.149048DOI Listing
July 2021

USP13-mediated IRAK4 deubiquitination disrupts the pathological symptoms of lipopolysaccharides-induced sepsis.

Microbes Infect 2021 Jul 20:104867. Epub 2021 Jul 20.

Department of Critical Care Medicine, People's Hospital of Xinjiang Uygur Autonomous Region, No.91 Tianchi Road, Tianshan District, Urumqi 830001, Xinjiang Uygur Autonomous Region, China. Electronic address:

Ubiquitin-specific peptidase 13 (USP13) has been reported to participate in tumorigenesis, cell cycle arrest, endoplasmic reticulum-associated degradation, and immune responses. Here, we explored the function of USP13 in pro-inflammatory cytokine production of macrophages and its role in mouse sepsis model. Primary bone-marrow-derived macrophages (BMDMs) isolated from wild type (WT) and USP13 mice were treated by lipopolysaccharides (LPS), IL-4, toll-like receptors (TLRs) agonists, and IRAK4 inhibitor to profile the inflammatory responses with different genotypes. Mouse sepsis model (WT and USP13) created by intraperitoneal injection with LPS plus D-galactosamine was used to assess septic shock-induced survival and lung inflammation. Flow cytometry, qRT-PCT, Western blot, and ELISA were performed to detect pro-inflammatory production and macrophage polarization. USP13 was a key regulator of IRAK4 deubiquitination in BMDMs and its myeloid specific deficiency contributed to LPS-induced pro-inflammatory response and septic symptoms. IRAK4 inhibitor co-administration improved in LPS-induced inflammatory responses in both BMDMs and septic mice. USP13 negatively regulates LPS-induced sepsis shock by targeting IRAK4. In summary, targeting USP13-IRAK4 axis might be a potential therapeutic strategy for the treatment of inflammation in sepsis shock.
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http://dx.doi.org/10.1016/j.micinf.2021.104867DOI Listing
July 2021

Integration of clinicopathological and mutational data offers insight into lung cancer with tumor spread through air spaces.

Ann Transl Med 2021 Jun;9(12):985

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: Tumor spread through air spaces (STAS) was defined as a unique tumor invasion pattern in adenocarcinoma (ADC) by The World Health Organization Classification of Lung Tumors in 2015. Since then, STAS had been shown to be associated with local recurrence and poor survival results, as the typical signature and potential mechanisms of STAS remained unclear. Our objectives were to comprehensively demonstrate the clinicopathological and genetic signatures in STAS-positive lung cancer patients.

Methods: The clinicopathological and gene alteration characteristics of 878 STAS-positive lung cancer patients were presented. Associations between parameters were evaluated using the Chi-square test, Fisher's exact test, and logistic regression. The capture-based targeted next generation sequencing (NGS) with a platform of 68 lung cancer-related genes was conducted in 139 cases, and the mutational spectrum was summarized.

Results: STAS was identified in 391 female and 481 male patients, of which ADC accounted for the majority of cases (92.6%). The concomitant solid or micropapillary subtype was observed in 92.12% patients with ADC. Poorly differentiated histological subtypes were more frequent and negatively correlated with tumor size in smaller tumor cases (P=0.036, Pearson's R=-0.075). Furthermore, in the subgroup of nodules within 3 cm, the distribution of the solid and micropapillary subtypes were significantly frequent in lymph node-positive patients (P<0.001). Tumor protein p53 (TP53) alterations were more frequent in smoking patients (27.6%, P=0.007), human epidermal growth factor receptor 2 (HER2) alterations were more common in female (10.8%, P=0.025), while Kirsten rat sarcoma viral oncogene (KRAS) (20.3%, P=0.024) and TP53 (45.9%, P=0.003) were more prevalent in males.

Conclusions: Poorly differentiated histological subtypes likely played a crucial role in promoting the invasiveness of STAS, especially in small tumor-size cases. Epidermal growth factor receptor (EGFR), TP53, KARS, anaplastic lymphoma kinase (ALK), and ROS proto-oncogene 1 (ROS1) were the five most frequent alterations in STAS-positive ADC.
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http://dx.doi.org/10.21037/atm-21-2256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267253PMC
June 2021

Target-swiped DNA lock for electrochemical sensing of miRNAs based on DNAzyme-assisted primer-generation amplification.

Mikrochim Acta 2021 07 15;188(8):255. Epub 2021 Jul 15.

Key Laboratory of Chemical Sensing & Analysis in Universities of Shandong, School of Chemistry and Chemical Engineering, University of Jinan, Jinan, 250022, People's Republic of China.

As an extremely important post-transcriptional regulator, miRNAs are involved in a variety of crucial biological processes, and the abnormal expressions of miRNAs are closely related to a variety of diseases. In this work, for the first time, we designed a nucleic acid lock nanostructure for specific detection of miRNA-21, which changes the self-structure to "active conformation" by binding the target, in order to generate triggers to initiate the subsequent reaction. Emphatically, this flexible nucleic acid lock is capable of self-cleaving without the assistance of external component, overcoming the disadvantages of the complex design and requiring protease assistance in traditional nanostructure. Moreover, the combination of DNAzyme and RCA technology not only greatly improves the efficiency of signal amplification but also enables primer generation to simultaneous cascade RCA amplification. Additionally, the electrochemical detection technology based on silver nanoclusters overcomes the shortcomings of traditional detection methods such as low sensitivity and complex operation. The detection limit achieved was 9.3 aM with a wide dynamic response ranging from 10 aM to 100 pM (at the DPV peak of - 0.5 V), which is comparable to most of the reported studies. Therefore, our work provided an ultra-sensitive way for the detection of miRNAs using nanostructures and revealed an effective means for disease theranostics and cancer diagnosis. In this work, for the first time, we designed a nucleic acid lock nanostructure based on its self-structural transformation for the specific detection of miRNA. And the combination of DNAzyme and cascade RCA reaction greatly improved the signal amplification efficiency.
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http://dx.doi.org/10.1007/s00604-021-04815-zDOI Listing
July 2021

Rapid electron transfer via dynamic coordinative interaction boosts quantum efficiency for photocatalytic CO reduction.

Nat Commun 2021 Jul 13;12(1):4276. Epub 2021 Jul 13.

KLGHEI of Environment and Energy Chemistry, School of Chemistry, Sun Yat-sen University, Guangzhou, China.

The fulfillment of a high quantum efficiency for photocatalytic CO reduction presents a key challenge, which can be overcome by developing strategies for dynamic attachment between photosensitizer and catalyst. In this context, we exploit the use of coordinate bond to connect a pyridine-appended iridium photosensitizer and molecular catalysts for CO reduction, which is systematically demonstrated by H nuclear magnetic resonance titration, theoretical calculations, and spectroscopic measurements. The mechanistic investigations reveal that the coordinative interaction between the photosensitizer and an unmodified cobalt phthalocyanine significantly accelerates the electron transfer and thus realizes a remarkable quantum efficiency of 10.2% ± 0.5% at 450 nm for photocatalytic CO-to-CO conversion with a turn-over number of 391 ± 7 and nearly complete selectivity, over 4 times higher than a comparative system with no additional interaction (2.4%±0.2%). Moreover, the decoration of electron-donating amino groups on cobalt phthalocyanine can optimize the quantum efficiency up to 27.9% ± 0.8% at 425 nm, which is more attributable to the enhanced coordinative interaction rather than the intrinsic activity. The control experiments demonstrate that the dynamic feature of coordinative interaction is important to prevent the coordination occupancy of labile sites, also enabling the wide applicability on diverse non-noble-metal catalysts.
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http://dx.doi.org/10.1038/s41467-021-24647-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277789PMC
July 2021

Identifying the Key Genes in Mouse Liver Regeneration After Partial Hepatectomy by Bioinformatics Analysis and / Experiments.

Front Genet 2021 23;12:670706. Epub 2021 Jun 23.

Department of Hepatobiliary Surgery, The Affiliated Hospital of Yunnan University, Kunming, China.

Background: The liver is the only organ that can completely regenerate after various injuries or tissue loss. There are still a large number of gene functions in liver regeneration that have not been explored. This study aimed to identify key genes in the early stage of liver regeneration in mice after partial hepatectomy (PH).

Materials And Methods: We first analyzed the expression profiles of genes in mouse liver at 48 and 72 h after PH from Gene Expression Omnibus (GEO) database. Gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) analysis were performed to identify key genes in liver regeneration. Finally, we validated key genes and .

Results: We identified 46 upregulated genes and 19 downregulated genes at 48 h after PH, and 223 upregulated genes and 40 downregulated genes at 72 h after PH, respectively. These genes were mainly involved in cell cycle, DNA replication, and p53 signaling pathway. Among of these genes, cycle-related genes (Ccna2, Cdkn1a, Chek1, and Mcm5) and Ube2c were highly expressed in the residual liver both at 48 and 72 h after PH. Furthermore, Ube2c knockdown not only caused abnormal expression of Ccna2, Cdkn1a, Chek1, and Mcm5, but also inhibited transition of hepatocytes from G1 to S phase of the cell cycle .

Conclusion: Mouse hepatocytes enter the proliferation phase at 48 h after PH. Ube2c may mediate cell proliferation by regulating or partially regulating Ccna2, Cdkn1a, Chek1, and Mcm5.
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http://dx.doi.org/10.3389/fgene.2021.670706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260846PMC
June 2021

Deferoxamine enhances the migration of dental pulp cells via hypoxia-inducible factor 1α.

Am J Transl Res 2021 15;13(5):4780-4787. Epub 2021 May 15.

Department of General Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; College of Stomatology, Shanghai Jiao Tong University; National Center for Stomatology; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology Shanghai, China.

In previous studies, we found that deferoxamine (DFO) improved the migration of dental pulp cells (DPCs). The present study aimed to determine whether the effects of DFO on the migration of DPCs were regulated via hypoxia-inducible factor 1α (HIF-1α). Recombinant adenovirus vectors carrying short hairpin RNA (shRNA) targeting the human HIF-1α gene (pAd-GFP-shRNA-HIF-1α) and green fluorescent protein (GFP) were constructed. The expression of HIF-1α was inhibited by pAd-GFP-shRNA-HIF-1α at messenger RNA and protein levels. The secretion of stromal cell-derived factor 1α (SDF-1α) or vascular endothelial growth factor (VEGF) in DPCs treated with 10 μM DFO was higher than that in the control condition. The migration of DPCs was enhanced by 10 μM DFO. However, the effects of DFO on DPCs were partially reversed by silencing the HIF-1α gene in enzyme-linked immunosorbent assay or migration assay. Cumulatively, we conclude that DFO upregulated the secretion of SDF-1α or VEGF in DPCs and improved the migration of DPCs through HIF-1α.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205705PMC
May 2021

Sulphur-Embedded Hydrocarbon Belts: Synthesis, Structure and Redox Chemistry of Cyclothianthrenes.

Angew Chem Int Ed Engl 2021 Aug 16;60(34):18443-18447. Epub 2021 Jul 16.

School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, China.

Cyclothianthrenes, a series of sulphur-embedded hydrocarbon belts proposed a decade ago, were successfully constructed through a stepwise bottom-up synthesis. The belt [6]cyclothianthrene ([6]CT) is the smallest and most strained member of the family yet reported. Both [6]CT and [8]CT are the first examples of cyclothianthrene characterized by single crystal X-ray diffraction. An unprecedented chiral belt [7]CT and a Möbius-shaped [9]CT were also achieved via modular synthesis. Crystallographic and computational studies show that belts [6]CT-[8]CT have prism-like conformations with well-defined tubular cavities which have potential for guest molecule inclusion. Cyclic voltammograms further revealed that these belts are redox-active. The success of constructing sulphur-embedded hydrocarbon belts, that is, cyclothianthrenes, greatly enriches the chemistry of heteroatom-doped molecular belts and tubes.
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http://dx.doi.org/10.1002/anie.202104054DOI Listing
August 2021

[Analysis of 137740 dental emergency cases from 2017 to 2018].

Shanghai Kou Qiang Yi Xue 2021 Apr;30(2):151-155

Department of General Dentistry, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology. Shanghai 200011, China.

Purpose: To analyze the clinical data of oral emergency cases and the characteristics of oral emergency diseases, and provide clinical basis for improving the quality of oral emergency treatment and making reasonable arrangement.

Methods: A total of 137 740 patients in oral emergency department from January 1st, 2017 to December 31st, 2018 were collected and analyzed retrospectively according to gender, age, time of visit and diagnosis. The results were analyzed with Chi-square test by Excel 7.0 and SPSS 19.0 software package.

Results: The ratio of men and women was 1.13:1, with an average age of 35.71 years. The highest incidence was seen in October 2018, and the lowest was in February 2017. The peak time of oral emergency was 20:00 to 21:00. The top three disease entity were maxillofacial injury (29.17%), facial infection (26.95%) and pulpitis (10.08%).

Conclusions: There is a wide range of diseases and a large number of patients in oral emergency and the visiting time is relatively concentrated. Dentists for emergency need to master the professional knowledge of oral surgery and endodontics. In order to make precise strategies to formulate the scale of oral emergency, considerations should be taken with the changing features of the period and month of oral emergency treatment.
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April 2021

Neutrophil Extracellular Traps and Macrophage Extracellular Traps Predict Postoperative Recurrence in Resectable Nonfunctional Pancreatic Neuroendocrine Tumors.

Front Immunol 2021 18;12:577517. Epub 2021 May 18.

Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Extracellular traps (ETs) and tumor-infiltrating immune cells can contribute to disease progression. The clinical significance of tumor-infiltrating neutrophils and macrophages and related extracellular traps in pancreatic neuroendocrine tumors (pNETs) has not been fully elucidated. This study aimed to explore the prognostic value of tumor infiltration and ET formation by neutrophils and macrophages in pNETs.

Methods: A total of 135 patients with radical resection of nonfunctional pNETs were analyzed retrospectively. Immunohistochemistry and immunofluorescence were utilized to stain tumor tissue sections. The recurrence-free survival (RFS) of subgroups determined by Kaplan-Meier analysis was compared with the log-rank test. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. A nomogram was established to predict 3-year RFS.

Results: Patients with high tumor-infiltrating neutrophils or macrophages or positive expression of neutrophils ETs or macrophage ETs displayed worse RFS (all p<0.05). Moreover, univariate and multivariate Cox regression analyses showed that neutrophil and macrophage infiltration and ETs were independent prognostic factors for RFS (all p<0.05). A combined parameter including WHO grade, TNM stage, tumor-infiltrating neutrophils and macrophages, and neutrophil and macrophage ETs had the highest C-index (0.866) and lowest Akaike information criteria (326.557). The calibration plot of nomogram composed of the combined parameter exhibited excellent prognostic values for 3-year RFS.

Conclusions: Infiltration and ETs by neutrophils and macrophages can be used as biological indicators of patient prognosis, suggesting the treatment potential for targeting those in nonfunctional pNETs.
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http://dx.doi.org/10.3389/fimmu.2021.577517DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168461PMC
June 2021

Subxiphoid versus Unilateral VATS Thymectomy for Thymomas: A Propensity Score-matching Analysis.

Ann Thorac Surg 2021 May 29. Epub 2021 May 29.

Department of Thoracic Surgery/Oncology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Disease, China State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou, PR China. Electronic address:

Background: The appropriate surgical approach of VATS for early-stage thymoma remains unclear. The present study aimed to explore the safety and feasibility of subxiphoid and subcostal arch thoracoscopic thymectomy in comparison with unilateral thoracoscopic thymectomy for treatment of early-stage thymoma.

Methods: The outcomes of 237 patients without myasthenia gravis who had undergone thoracoscopic thymectomy for Masaoka stage I and II thymoma from January 2015 to May 2019 at our center were retrospectively evaluated (subxiphoid and subcostal arch approach: 39; unilateral VATS approach: 198). A propensity score-matching analysis was generated to control for selection bias due to nonrandom group assignment in a 1:1 manner.

Results: There was no surgery-related mortality in included patients. Matching of patients according to propensity score resulted in a cohort that consisted of 39 patients in both groups. Patients had similar clinical characteristics in both groups. Compared with those in the unilateral group, patients in the subxiphoid group yielded lower pain scores at 24- and 72-hours post-operation, respectively (P<0.01). In addition, the operation time was longer in the subxiphoid group (147.5±43.6min vs. 93.2±33.8min, p<0.01). There were no significant differences in blood loss, total volume and time of drainage, complications or postoperative hospital stays between the two groups.

Conclusions: Subxiphoid and subcostal arch thoracoscopic thymectomy for early-stage thymoma appears to be a safe and feasible procedure. It is considered to be less invasive as it may cause minimal postoperative pain compared to the unilateral VATS approach.
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http://dx.doi.org/10.1016/j.athoracsur.2021.05.011DOI Listing
May 2021

Construction of Buertai Coal Macromolecular Model and GCMC Simulation of Methane Adsorption in Micropores.

ACS Omega 2021 May 20;6(17):11173-11182. Epub 2021 Apr 20.

College of Chemistry and Chemical Engineering, Xi'an University of Science and Technology, Xi'an 710054, Shaanxi, China.

With the increase in high gas mines in the low coal rank mining area in the northwestern part of China, high gas mines in the low-rank coal mining area have caused many gas emission accidents. Coal is a porous material, containing a large number of micropores (<2 nm), which can absorb large amounts of methane, so it is necessary to explore methane adsorption in micropores of low-rank coal. In this work, FTIR, HRTEM, and C-NMR were used to test the macromolecular structural parameters of Buertai coal, which was a kind of low-rank Jurassic coal in northwestern China. The results showed that the aromatic structural units in the Buertai coal structure mainly consist of naphthalene, anthracene, and phenanthrene. The fat structure mainly occurs in the form of aliphatic side chains, cycloalkanes, and other compounds. The oxygen atoms are present in the form of carbonyl groups, ether bonds, and phenol groups with a ratio of about 6:4:9. The nitrogen atoms are present in the form of pyrrole and pyridine compounds. Finally, the macromolecular structure model of Buertai coal was built, and the calculated NMR spectrum from the model was very consistent with the experimental NMR spectrum of Buertai coal. The relationship between the macromolecular density and energy of Buertai coal was explored using the Amorphous Cell module in the simulation software, Materials Studios 8.0 (MS 8.0), and the density value at the lowest energy was determined to be about 1.23 g/cm. The pore structure parameters of Buertai coal were also calculated. It was found that both pore volume and void fraction decreased evenly as the diameter of the probe molecule increased, but the surface area decreased rapidly when the diameter of the probe molecule was 3.46 Å. All pore sizes were found to be smaller than 10 Å from the pore size distribution (PSD) curve of Buertai coal, which provided a lot of adsorption sites for methane (CH). The results of the CH adsorption simulation from Grand Canonical Monte Carlo (GCMC) showed that CH is adsorbed inside the micropores of coal, and the adsorption capacity of CH depends on the diameters of micropores when the micropores are less than 8.5 Å. There are many micropores where CH did not appear because these micropores are closed and did not provide a channel for CH to enter. The results of experimental methane adsorption indicate that the excess adsorption capacity from the GCMC simulation was very close to the experimental results of Buertai coal. This work provides a new perspective to study the methane adsorption behavior in micropores of coal.
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http://dx.doi.org/10.1021/acsomega.0c04649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153943PMC
May 2021

Integrated analysis of microRNA and mRNA expression profiles in homozygous familial hypercholesterolemia patients and validation of atherosclerosis associated critical regulatory network.

Genomics 2021 Jul 28;113(4):2572-2582. Epub 2021 May 28.

Department of Biochemistry and Molecular Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address:

Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening genetic disorder characterized by an extremely elevated serum level of low-density lipoprotein cholesterol (LDL-C) and accelerated premature atherosclerotic cardiovascular diseases (ASCVD). However, the detailed mechanism of how the pathogenic mutations of HoFH trigger the acceleration of ASCVD is not well understood. Therefore, we performed high-throughput RNA and small RNA sequencing on the peripheral blood RNA samples of six HoFH patients and three healthy controls. The gene and miRNA expression differences were analyzed, and seven miRNAs and six corresponding genes were screened out through regulatory network analysis. Validation through quantitative PCR of genes and miRNAs from 52 HoFH patients and 20 healthy controls revealed that the expression levels of hsa-miR-486-3p, hsa-miR-941, and BIRC5 were significantly upregulated in HoFH, while ID1, PLA2G4C, and CACNA2D2 were downregulated. Spearman correlation analysis found that the levels of ID1, hsa-miR-941, and hsa-miR-486-3p were significantly correlated with additional ASCVD risk factors in HoFH patients. This study represents the first integrated analysis of transcriptome and miRNA expression profiles in patients with HoFH, a rare disease, and as a result, six differentially expressed miRNAs/genes that may be related to atherosclerosis in HoFH are reported. The miRNA-mRNA regulatory network may be the critical regulation mechanism by which ASCVD is accelerated in HoFH.
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http://dx.doi.org/10.1016/j.ygeno.2021.05.036DOI Listing
July 2021

Cytidine Deaminase APOBEC3A Regulates PD-L1 Expression in Cancer Cells in a JNK/c-JUN-Dependent Manner.

Mol Cancer Res 2021 Sep 27;19(9):1571-1582. Epub 2021 May 27.

Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor, Michigan.

Programmed death-ligand 1 (PD-L1) promotes tumor immune evasion by engaging the PD-1 receptor and inhibiting T-cell activity. While the regulation of PD-L1 expression is not fully understood, its expression is associated with tumor mutational burden and response to immune checkpoint therapy. Here, we report that Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) is an important regulator of expression. Using an APOBEC3A inducible expression system as well as siRNA against endogenous APOBEC3A, we found that APOBEC3A regulates PD-L1 mRNA and protein levels as well as PD-L1 cell surface expression in cancer. Mechanistically, APOBEC3A-induced PD-L1 expression was dependent on APOBEC3A catalytic activity as catalytically dead APOBEC3A mutant (E72A) failed to induce PD-L1 expression. Furthermore, APOBEC3A-induced PD-L1 expression was dependent on replication-associated DNA damage and JNK/c-JUN signaling but not interferon signaling. In addition, we confirmed the relevance of these finding in patient tumors as APOBEC3A expression and mutational signature correlated with expression in multiple patient cancer types. These data provide a novel link between APOBEC3A, its DNA mutagenic activity and PD-L1-mediated antitumoral immunity. This work nominates APOBEC3A as a mechanism of immune evasion and a potential biomarker for the therapeutic efficacy of immune checkpoint blockade. IMPLICATIONS: APOBEC3A catalytic activity induces replication-associated DNA damage to promote PD-L1 expression implying that APOBEC3A-driven mutagenesis represents both a mechanism of tumor immune evasion and a therapeutically targetable vulnerability in cancer cells.
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http://dx.doi.org/10.1158/1541-7786.MCR-21-0219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419025PMC
September 2021

lncRNA TUG1 inhibits the cancer stem cell‑like properties of temozolomide‑resistant glioma cells by interacting with EZH2.

Mol Med Rep 2021 Jul 26;24(1). Epub 2021 May 26.

Department of Neurosurgery, First People's Hospital of Kunming, Kunming, Yunnan 650032, P.R. China.

Temozolomide (TMZ) is currently one of the first‑line drugs used for the treatment of high‑grade gliomas. However, TMZ resistance results in unsatisfactory therapeutic effects in gliomas. Cancer stem cells (CSCs) have recently been determined to serve a pivotal regulatory role in tumor metastasis, recurrence and chemoresistance. In addition, numerous reports have shown that long non‑coding RNAs (lncRNAs) exert an essential role in the occurrence and development of tumors, and can be used as biomarkers for tumor diagnosis and treatment. Among them, studies have revealed that taurine upregulated gene 1 (TUG1) exhibits an important regulatory effect on the malignant biological behavior of glioma cells. Moreover, it has been reported that enhancer of Zeste homolog 2 polycomb repressive complex subunit 2 (EZH2) promotes tumorigenesis, including in glioma. However, the underlying mechanism of the interaction of TUG1 and EZH2 with CSCs of glioma remains elusive, and thus requires further clarification. The present study aimed to explore the role of TUG1 and EZH2 in TMZ resistance in glioma. Cell Counting Kit‑8, colony formation,sphere formation and Annexin V‑FITC/PI assays were used to detect the proliferation, clone formation efficiency, stemness and apoptosis of TMZ‑resistant glioma cells. Xenograft tumor assay was used to detect the effect of TUG1 on the tumorigenesis of TMZ‑resistant glioma cells. The present findings demonstrated that TUG1 exhibited a low expression in glioma cells, while EZH2 expression was the opposite. Moreover, it was observed that A172/TMZ cells possessed higher CSCs‑like properties compared with parent cells, and that TUG1 and EZH2 were abnormally expressed in A172/TMZ cells. Knockdown of TUG1 or overexpression of EZH2 promoted A172/TMZ cell proliferation and CSCs‑like properties, as well as inhibited their apoptosis, thereby enhancing the TMZ resistance of A172/TMZ cells. Furthermore, it was found that TUG1 alleviated the TMZ resistance of A172/TMZ cells by inhibiting EZH2 expression. Of note, overexpression of TUG1 inhibited the tumorigenicity of A172/TMZ cells by downregulating EZH2 expression in vivo. Collectively, the present study demonstrated that TUG1 served an essential regulatory role in TMZ resistance of gliomas.
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http://dx.doi.org/10.3892/mmr.2021.12172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170197PMC
July 2021

Risk Factors for the Development of Intraoperative Hypoxia in Patients Undergoing Nonintubated Video-Assisted Thoracic Surgery: A Retrospective Study from a Single Center.

Med Sci Monit 2021 Apr 26;27:e928965. Epub 2021 Apr 26.

Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China (mainland).

BACKGROUND Nonintubated video-assisted thoracic surgery (NIVATS) has been demonstrated to be safe and effective in patients. However, the risk factors for intraoperative hypoxia are unclear. This retrospective study aimed to identify the risk factors for the development of intraoperative hypoxia in patients undergoing NIVATS. MATERIAL AND METHODS The study included patients who underwent NIVATS between January 2011 and December 2018. Intraoperative hypoxia was defined as SpO₂ ≤93%. Risk factors for hypoxia were identified by binary logistic regression analysis, and the characteristic distribution of patients with and without hypoxia was elaborated. RESULTS Of 2742 included patients, age, anesthesia method, the technical level of surgeons, stair-climbing ability, and type of thoracic procedure were associated with intraoperative hypoxia (P<0.05). The characteristics of patients with hypoxia were older age (P=0.011), higher body mass index and revised cardiac risk index level (P=0.033 and P=0.031), and lower composition of stair-climbing ≥22 m (P<0.001). These patients also had more anatomical lung surgery and mediastinal mass resection (P=0.033) and more epidural anesthesia (P=0.005). The surgeries were more likely to be performed by surgeons with less than 10 years of VATS training (P=0.009) and to have increased intraoperative maximum end-expiratory carbon dioxide partial pressure (P<0.001). These patients had a longer Intensive Care Unit stay (P<0.001), duration of chest-tube drainage (P=0.019), and postoperative hospitalization (P=0.003). CONCLUSIONS The current study suggests that old age and stair-climbing ability of patients, anesthesia method, thoracic procedures, and surgeon experience are risk factors for intraoperative hypoxia in patients undergoing NIVATS.
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http://dx.doi.org/10.12659/MSM.928965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086517PMC
April 2021

KCNN4 promotes the progression of lung adenocarcinoma by activating the AKT and ERK signaling pathways.

Cancer Biomark 2021 ;31(2):187-201

Department of Pathology, School of Basic Medical Sciences and Sir Run Run Hospital and Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing, Jiangsu, China.

Background: Potassium channels, encoded by more than seventy genes, are cell excitability transmembrane proteins and become evident to play essential roles in tumor biology.

Objective: The deregulation of potassium channel genes has been related to cancer development and patient prognosis. The objective of this study is to understand the role of potassium channels in lung cancer.

Methods: We examined all potassium channel genes and identified that KCNN4 is the most significantly overexpressed one in lung adenocarcinoma. The role and mechanism of KCNN4 in lung adenocarcinoma were further investigated by in vitro cell and molecular assay and in vivo mouse xenograft models.

Results: We revealed that the silencing of KCNN4 significantly inhibits cell proliferation, migration, invasion, and tumorigenicity of lung adenocarcinoma. Further studies showed that knockdown of KCNN4 promotes cell apoptosis, induces cell cycle arrested in the S phase, and is associated with the epithelial to mesenchymal transition (EMT) process. Most importantly, we demonstrated that KCNN4 regulates the progression of lung adenocarcinoma through P13K/AKT and MEK/ERK signaling pathways. The use of inhibitors that targeted AKT and ERK also significantly inhibit the proliferation and metastasis of lung adenocarcinoma cells.

Conclusions: This study investigated the function and mechanism of KCNN4 in lung adenocarcinoma. On this basis, this means that KCNN4 can be used as a tumor marker for lung adenocarcinoma and is expected to become an important target for a potential drug.
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http://dx.doi.org/10.3233/CBM-201045DOI Listing
January 2021

Non-intubated video-assisted thoracic surgery for subxiphoid anterior mediastinal tumor resection.

Ann Transl Med 2021 Mar;9(5):403

Department of Thoracic Surgery and Oncology, the First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, Guangzhou, China.

Background: Subxiphoid approach for mediastinal tumor resection was reported to provide a better view and less postoperative pain. Non-intubated video-assisted thoracic surgery (NI-VATS) without muscle relaxant would decrease the possibility of postoperative airway collapse for anterior mediastinal mass operation. Herein, we sought to describe the use of NI-VATS through subxiphoid approach for anterior mediastinal tumor resection.

Methods: In this retrospective cohort study, patients that underwent subxiphoid VATS resection for anterior mediastinal tumor between December 2015 and September 2019 were divided into two groups: NI-VATS and intubated VATS (I-VATS). Intraoperative and postoperative variables were compared.

Results: A total of 40 patients were included. Among them, 21 patients received NI-VATS (52.5%) and 19 were treated with I-VATS (47.5%). In total, intraoperative (4/21 . 2/19; P=0.446) and postoperative complications (5/21 . 7/19; P=0.369) were similar between NI-VATS and I-VATS group. The anesthesia time (231.76 . 244.71 min; P=0.218), the operation time (152.35 . 143.64 min; P=0.980), chest tube duration (1.81 . 1.84 days; P=0.08), the total volume (351.95 . 348.00 mL; P=0.223), post-operative pain scores (2.79 . 2.93, P=0.413), and the length of stay (9.47 . 10.57 days; P=0.970) were all comparable between two groups.

Conclusions: NI-VATS for mediastinal tumor resection via subxiphoid approach is a safe and technically feasible option in selected patients, which leads to comparable perioperative clinical outcomes when compared with I-VATS via the subxiphoid approach. This technique could be used as an alteration when intubation is not available.
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http://dx.doi.org/10.21037/atm-20-6125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033331PMC
March 2021

Agomelatine prevents macrophage infiltration and brain endothelial cell damage in a stroke mouse model.

Aging (Albany NY) 2021 04 4;13(10):13548-13559. Epub 2021 Apr 4.

Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.

Background And Purpose: Ischemic/reperfusions are regarded as the clinical consensus for stroke treatment, which results in secondary injury of brain tissues. Increased blood-brain barrier (BBB) permeability and infiltration of inflammatory cells are responsible for the ischemic/reperfusion injury. In the present study, we aimed to investigate the effects of Agomelatine on brain ischemic/reperfusions injury and the underlying mechanism.

Methods: MCAO model was established in mice. The expressions of CD68 and claudin-5 in the cerebral cortex were determined using an immunofluorescence assay. Brain permeability was evaluated using Evans blue staining assay. A two-chamber and two-cell trans-well assay was used to detect the migration ability of macrophages through endothelial cells. The expression levels of claudin-5 and MCP-1 in the endothelial cells were determined using qRT-PCR and ELISA.

Results: CD68 was found to be up-regulated in the cerebral cortex of MCAO mice but was down-regulated by treatment with Agomelatine. The expression level of down-regulated claudin-5 in the cerebral cortex of MCAO mice was significantly suppressed by Agomelatine. Deeper staining of Evans blue was found in the MCAO group, which was however faded significantly in the Agomelatine treated MCAO mice. The migrated macrophages were significantly increased by hypoxia incubation but were greatly suppressed by the introduction of Agomelatine. The down-regulated claudin-5 by hypoxic incubation in endothelial cells was up-regulated by treatment with Agomelatine. Furthermore, the increased expression of MCP-1 in endothelial cells under hypoxic conditions was significantly inhibited by Agomelatine.

Conclusion: Agomelatine prevents macrophage infiltration and brain endothelial cell damage in a stroke mouse model.
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http://dx.doi.org/10.18632/aging.202836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202857PMC
April 2021

Successful treatment of upper-left eyelid squamous cell carcinoma in an epidermodysplasia verruciformis patient by ALA-PDT/holmium laser combination therapy.

Photodiagnosis Photodyn Ther 2021 Jun 2;34:102277. Epub 2021 Apr 2.

Institute of Photomedicine, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address:

Epidermodysplasia verruciformis (EV) is a rare autosomal recessive disorder. Individuals with EV are more susceptible to the development of cutaneous neoplasia in sun-exposed regions. This disease should be closely observed for cutaneous squamous cell carcinoma (cSCC) or pre-cancerous lesions - if neoplasia is found, it should be removed. A 68-year-old woman with EV had a post-operative recurrent, invasive cSCC growing on her upper-left eyelid. Although the standard treatment for cSCC is surgical excision, it is challenging to reach the deepest regions. Herein, we reported a case of a recurrent, invasive cSCC effectively treated by a combination of non-invasive 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) and deep-penetrative holmium laser. The results were satisfactory without any adverse effects to the patient.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102277DOI Listing
June 2021
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