Publications by authors named "Lin Xu"

2,415 Publications

  • Page 1 of 1

VATS Versus Open Lobectomy in Pathological T1 SCLC: A Multi-Center Retrospective Analysis.

Clin Lung Cancer 2021 Jun 24. Epub 2021 Jun 24.

Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. Electronic address:

Background: Video-assisted thoracic surgery (VATS) has been widely used in the surgical treatment of thoracic diseases, and it suggested surgical and oncological advantages compared with open surgery. However, reports on the application of VATS in surgery of small cell lung cancer (SCLC) are scarce. This study aimed to explore the advantages and disadvantages of different surgical approaches in the treatment of pathological stage T1(pT1) SCLC in terms of safety, clinical outcomes, and lymph node dissection.

Patients And Methods: Patients who underwent lobectomy for pT1 SCLC between January 2014 and September 2017 were identified from the National Collaborative Lung Cancer Database (LinkDoc Database). The patients were stratified based on the surgery approach (VATS or open lobectomy). Perioperative outcomes and long-term survival were analyzed using SPSS software.

Results: A total of 169 patients with pT1 SCLC met the criteria and were enrolled for this study, including 110 cases of VATS lobectomies and 59 cases of open lobectomies. VATS lobectomy was associated with less blood loss than open surgery (168.1 ± 237.4 vs. 340.0 ± 509.8 mL, P = .002). Open lobectomy harvested more N2 LNs (11.8 ± 8.2 vs. 8.4 ± 5.8, P = .048) and identified more metastasis positive LNs (3.1 ± 6.0 vs. 1.4 ± 3.0, P = .050). Open lobectomy associated with longer overall survival (OS) but has no statistical difference (23.4 ± 13.2 vs. 20.2 ± 10.9, P = .070).

Conclusion: Open lobectomy had better lymph node dissection results, and comparable postoperative complications, postoperative hospital stay, and OS to VATS lobectomy. Further studies may still be needed to confirm the recommendation of thoracoscopic approach as a routine surgical procedure for operable SCLC, and until then, open surgery should still be considered.
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http://dx.doi.org/10.1016/j.cllc.2021.06.007DOI Listing
June 2021

Icotinib versus chemotherapy as adjuvant treatment for stage II-IIIA EGFR-mutant non-small-cell lung cancer (EVIDENCE): a randomised, open-label, phase 3 trial.

Lancet Respir Med 2021 Jul 16. Epub 2021 Jul 16.

Thoracic Surgery Department, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Background: Icotinib has provided survival benefits for patients with advanced, epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC). We aimed to compare icotinib with chemotherapy in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection. Here, we report the results from the preplanned interim analysis of the study.

Methods: In this multicentre, randomised, open-label, phase 3 trial done at 29 hospitals in China, eligible patients were aged 18-70 years, had histopathogically confirmed stage II-IIIA NSCLC, had complete resection up to 8 weeks before random assignment, were treatment-naive, and had confirmed activation mutation in exon 19 or exon 21 of the EGFR gene. Participants were randomly assigned (1:1) with an interactive web-based response system to receive either oral icotinib 125 mg thrice daily for 2 years or four 21-day cycles of intravenous chemotherapy (vinorelbine 25 mg/m on days 1 and 8 of each cycle plus cisplatin 75 mg/m on day 1 of each cycle for adenocarcinoma or squamous carcinoma; or pemetrexed 500 mg/m plus cisplatin 75 mg/m on day 1 every 3 weeks for non-squamous carcinoma). The primary endpoint was disease-free survival assessed in the full analysis set. Secondary endpoints were overall survival assessed in the full analysis set and safety assessed in all participants who received study drug. This trial is registered with ClinicalTrials.gov, NCT02448797.

Findings: Between June 8, 2015, and August 2, 2019, 322 patients were randomly assigned to icotinib (n=161) or chemotherapy (n=161); the full analysis set included 151 patients in the icotinib group and 132 in the chemotherapy group. Median follow-up in the full analysis set was 24·9 months (IQR 16·6-36·4). 40 (26%) of 151 patients in the icotinib group and 58 (44%) of 132 patients in the chemotherapy group had disease relapse or death. Median disease-free survival was 47·0 months (95% CI 36·4-not reached) in the icotinib group and 22·1 months (16·8-30·4) in the chemotherapy group (stratified hazard ratio [HR] 0·36 [95% CI 0·24-0·55]; p<0·0001). 3-year disease-free survival was 63·9% (95% CI 51·8-73·7) in the icotinib group and 32·5% (21·3-44·2) in the chemotherapy group. Overall survival data are immature with 14 (9%) deaths in the icotinib group and 14 (11%) deaths in the chemotherapy. The HR for overall survival was 0·91 (95% CI 0·42-1·94) in the full analysis set. Treatment-related serious adverse events occurred in two (1%) of 156 patients in the icotinib group and 19 (14%) of 139 patients in the chemotherapy group. No interstitial pneumonia or treatment-related death was observed in either group.

Interpretation: Our results suggest that compared with chemotherapy, icotinib significantly improves disease-free survival and has a better tolerability profile in patients with EGFR-mutant stage II-IIIA NSCLC after complete tumour resection.

Funding: Betta Pharmaceuticals TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S2213-2600(21)00134-XDOI Listing
July 2021

The Long Noncoding RNA LINC00665 Facilitates c-Myc Transcriptional Activity the miR-195-5p MYCBP Axis to Promote Progression of Lung Adenocarcinoma.

Front Oncol 2021 1;11:666551. Epub 2021 Jul 1.

Department of Thoracic Surgery, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.

Long noncoding RNAs (lncRNAs) have recently received growing substantial attention in cancer research due to their important roles in various cancer types. However, the underlying mechanisms and functions of lncRNAs, especially in lung adenocarcinoma (LUAD), remain elusive. Based on pan-cancer screening analyses, we identified that the noncoding RNA LINC00665 was up-regulated in lung adenocarcinoma, which was subsequently confirmed in clinical samples and cell lines. Higher expression of LINC00665 was positively associated with poor prognosis and advanced T stage. Next, using gain- and loss- of function approaches, we revealed that LINC00665 promotes cell proliferation, cell migration, invasion, and suppresses cell apoptosis in LUAD through and experiments. Additionally, our findings showed that LINC00665 was predominately localized in the cytoplasm so as to interact with Ago2 protein, which could function as miRNA sponges. The results of bioinformatics prediction and RNA pull-down assay indicated that LINC00665 directly interacted with miR-195-5p. This was also confirmed by fluorescence colocalization. Furthermore, luciferase reporter assay demonstrated that Myc binding protein (MYCBP, also called AMY-1), which enhanced c-Myc transcriptional activity, was the target gene of LINC00665 dependent on miR-195-5p. Finally, rescue functional assay results uncovered that the oncogenic capability of LINC00665 was dependent on miR-195-5p and c-Myc transcriptional activity. In summary, this work elucidates that LINC00665 accelerates LUAD progression the miR-195-5p/MYCBP axis by acting as a competing endogenous RNA (ceRNA), suggesting that LINC00665 may represent a potential therapeutic target for clinical intervention of LUAD.
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http://dx.doi.org/10.3389/fonc.2021.666551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281894PMC
July 2021

Clinical study of 3D printed personalized prosthesis in the treatment of bone defect after pelvic tumor resection.

J Orthop Translat 2021 Jul 30;29:163-169. Epub 2021 Jun 30.

Guangxi Medical University, Guangxi Zhuang Autonomous Region, Nanning 530021, China.

Background: /Objective: In recent years, prostheses have been widely used for limb reconstruction after pelvic tumour resection. However, prostheses are associated with problems leading to tumour recurrence, poor implant matching, defects after tumour resection, and easy implant looseness or failure. To achieve a precise preoperative design, complete tumour resection, and better anatomical structure matching and prosthesis stability, this study used three-dimensionally (3D)-printed osteotomy guides and personalised prostheses for reconstruction after pelvic tumour resection. This study aimed to explore the early clinical efficacy of 3D printed personalised prostheses for the reconstruction of bone defects after pelvic tumour resection.

Methods: A total of 20 patients (12 males, 8 females) with pelvic tumours surgically treated at our hospital between October 2014 and October 2019 were selected. There were 10 cases each of giant cell bone tumours and osteochondrosarcomas. According to Enneking zoning, there were 11 and 9 cases with tumours located in zones I and II, respectively. All cases were equally divided into conventional and 3D printing groups. For repair and reconstruction, a nail rod system or a steel plate was used in the conventional group while individualised 3D-printed prostheses were used in the 3D printing group. The surgical incision, duration of surgery, intraoperative blood loss, and the negative rate of resection margins in postoperative tumour specimens were examined. The follow-up focused on tumour recurrence, complications, and the Musculoskeletal Tumor Society (MSTS) score.

Results: All cases were followed-up for 6-24 months. The average incision length, duration of surgery, amount of intraoperative blood loss, and MSTS score of the 3D printing group were 10.0 ± 3.1 cm, 115.2 ± 25.3 min, 213.2 ± 104.6 mL, 23.8 ± 1.3, respectively, and those of the conventional group were 19.8 ± 8.4 cm, 156.8 ± 61.4 min, 361.4 ± 164.2 mL, and 18.3 ± 1.4, respectively. Histological tumour specimen examination showed nine and three cases with negative resection margins in the 3D printing group and the conventional group, respectively. The abovementioned indicators were significantly different between both groups ( < 0.05).

Conclusion: Applying 3D printed surgical guides and personalised prostheses for pelvic tumour resection, repair, and reconstruction, as well as preoperative planning and design, enables more accurate tumour resections and better prosthesis-patient matchings, possibly reducing surgical trauma, shortening the duration of surgery, and promoting the functional recovery of patients postoperatively.

The Translation Potential Of This Article: Contrary to existing studies on 3D printed personalised prostheses, this study reports the clinical efficacy of the aforementioned technology in treating bone defects in a series of patients who underwent pelvic tumour resection. Moreover, it presents a comprehensive comparison of this technology with conventional procedures, thus strengthening its importance in treatment regimens for reconstructing bone defects.
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http://dx.doi.org/10.1016/j.jot.2021.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258599PMC
July 2021

Expression of Autophagy-Related Factors LC3A and Beclin 1 and Apoptosis-Related Factors Bcl-2 and BAX in Osteoblasts Treated With Sodium Fluoride.

Front Physiol 2021 1;12:603848. Epub 2021 Jul 1.

Department of Pathology, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Objective: This study aims to analyze the expressions of autophagy-related factors light chain 3 alpha (LC3A) and Beclin 1 and apoptosis-related factors B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (BAX) in primary osteoblasts treated with sodium fluoride (NaF).

Methods: Osteoblasts were extracted from Sprague-Dawley rats and treated with 0, 2.5, 5, and 10 mg/L NaF solutions, followed by 10 mmol/L 3-methyladenine (3-MA) for 24 h. The apoptotic rate was determined by flow cytometry, and the expressions of the autophagy- and apoptosis-related factors were measured by western blotting and real-time quantitative polymerase chain reaction.

Results: The mRNA expressions of LC3A, Beclin 1, and BAX in the NaF-treated osteoblast group were higher than those in the control group, while the protein expressions of these factors in the NaF-treated group were significantly higher than those in the control group. However, the Bcl-2 protein expression in the NaF-treated osteoblasts was significantly decreased compared to that in the control cells. After the 3-MA treatment, the protein expressions of LC3A, Beclin 1, and Bcl-2 were significantly decreased compared with those of the NaF-treated group, whereas the expression of BAX increased. Moreover, the apoptosis rate was increased after the addition of the 3-MA inhibitor.

Conclusion: NaF stimulation promoted autophagy and apoptosis of the osteoblasts, suggesting the involvement of fluoride damage in these processes.
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http://dx.doi.org/10.3389/fphys.2021.603848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281676PMC
July 2021

Remdesivir Inhibits Tubulointerstitial Fibrosis in Obstructed Kidneys.

Front Pharmacol 2021 2;12:626510. Epub 2021 Jul 2.

Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Kidney impairment is observed in patients with COVID-19. The effect of anti-COVID-19 agent remdesivir on kidneys is currently unknown. We aimed to determine the effect of remdesivir on renal fibrosis and its downstream mechanisms. Remdesivir and its active nucleoside metabolite GS-441524 were used to treat TGF-β stimulated renal fibroblasts (NRK-49F) and human renal epithelial (HK2) cells. Vehicle or remdesivir were given by intraperitoneal injection or renal injection through the left ureter in unilateral ureteral obstruction (UUO) mice. Serum and kidneys were harvested. The concentrations of remdesivir and GS-441524 were measured using LC-MS/MS. Renal and liver function were assessed. Renal fibrosis was evaluated by Masson's trichrome staining and Western blotting. Remdesivir and GS-441524 inhibited the expression of fibrotic markers (fibronectin and aSMA) in NRK-49F and HK2 cells. Intraperitoneal injection or renal injection of remdesivir attenuated renal fibrosis in UUO kidneys. Renal and liver function were unchanged in remdesivir treated UUO mice. Two remdesivir metabolites were detected after injection. Phosphorylation of Smad3 that was enhanced in cell and animal models for renal fibrosis was attenuated by remdesivir. In addition, the expression of Smad7, an anti-fibrotic factor, was increased after remdesivir treatment and . Moreover, knockdown of Smad7 blocked the antifibrotic effect of GS and RDV on renal cells. Remdesivir inhibits renal fibrosis in obstructed kidneys.
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http://dx.doi.org/10.3389/fphar.2021.626510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284048PMC
July 2021

Association of a composite score of relative grip strength and timed up and go test with incident type 2 diabetes mellitus: Guangzhou Biobank Cohort Study.

Aging (Albany NY) 2021 Jul 16;13(undefined). Epub 2021 Jul 16.

School of Public Health, Sun Yat-Sen University, Guangzhou, China.

Background: We investigated association of a score incorporating relative grip strength (RGS) and timed up and go (TUG) test with incident type 2 diabetes mellitus (T2DM) in older Chinese.

Methods: Both RGS and TUG scores were classified into tertiles (0~2 points) and summed to yield RGS-TUG score, ranging from 0 to 4 points, with higher points indicating better physical function. Cox proportional hazards regression was used to analyze association of RGS-TUG score with incident T2DM.

Results: 3,892 participants without T2DM were followed up for an average of 3.6 years with 240 developing T2DM. After adjustment, those with the lowest RGS-TUG score, versus the highest, had higher fasting glucose, two-hour post-load glucose and glycosylated hemoglobin A1c, with β (95% confidence interval (CI)) being 0.21 (0.08, 0.33), 1.06 (0.69, 1.43) and 0.16 (0.06, 0.27), respectively. In participants with BMI of ≥25 kg/m2, those with the lowest RGS-TUG score showed a higher risk of T2DM (adjusted hazard ratio 3.01, 95% CI 1.04-8.69). No association was found for BMI of 18.5~<25 kg/m2 (P for interaction < 0.05).

Conclusions: This is the first study showing lower RGS-TUG score was associated with increased glycemia and incident T2DM in older people with overweight/obesity. The underlying mechanisms warrant further investigation.
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http://dx.doi.org/10.18632/aging.203285DOI Listing
July 2021

Lipidomics reveals association of circulating lipids with body mass index and outcomes in IgA nephropathy patients.

J Mol Cell Biol 2021 Jul 17. Epub 2021 Jul 17.

Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai 200031, China.

IgA nephropathy (IgAN) is a leading cause of chronic kidney disease (CKD), which are commonly accompanied by dyslipidemia. Obesity is also associated with dyslipidemia and risk of CKD, but the relation of the dyslipidemia patterns with obesity and disease progression in IgAN patients remains unknown. Traditional Chinese medicine (TCM) and the combined treatment with corticosteroids and TCM have been shown to be of benefit for IgAN patients, but predictive markers for guiding these treatments are lacking. Here, we quantified 545 lipid species in the plasma from 196 participants, including 140 IgAN patients and 56 healthy volunteers, and revealed an altered plasma lipidome in IgAN patients as compared to healthy participants. Association analysis showed that a sub-group of glycerides, particularly triacylglycerols (TGs) containing docosahexaenoic acid, were positively associated with high body mass index (BMI) in under- or normal weight IgAN patients, while several free fatty acids and sphingomyelins were positively associated with high BMI in overweight or obese IgAN patients. Further, our study suggested that elevated levels of eight lipids, mainly TG species containing linolenic acid, were independent risk factors for IgAN progression and also reported the prospective association of circulating lipids with treatment outcomes in IgAN. Taken together, our findings may not only help to achieve precision medicine but also provide a knowledge base for dietary intervention in the treatment of IgAN.
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http://dx.doi.org/10.1093/jmcb/mjab040DOI Listing
July 2021

Depdc5 deficiency exacerbates alcohol-induced hepatic steatosis via suppression of PPARα pathway.

Cell Death Dis 2021 Jul 15;12(7):710. Epub 2021 Jul 15.

Department of Medical Genetics, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.

Alcohol-related liver disease (ALD), a condition caused by alcohol overconsumption, occurs in three stages of liver injury including steatosis, hepatitis, and cirrhosis. DEP domain-containing protein 5 (DEPDC5), a component of GAP activities towards Rags 1 (GATOR1) complex, is a repressor of amino acid-sensing branch of the mammalian target of rapamycin complex 1 (mTORC1) pathway. In the current study, we found that aberrant activation of mTORC1 was likely attributed to the reduction of DEPDC5 in the livers of ethanol-fed mice or ALD patients. To further define the in vivo role of DEPDC5 in ALD development, we generated Depdc5 hepatocyte-specific knockout mouse model (Depdc5-LKO) in which mTORC1 pathway was constitutively activated through loss of the inhibitory effect of GATOR1. Hepatic Depdc5 ablation leads to mild hepatomegaly and liver injury and protects against diet-induced liver steatosis. In contrast, ethanol-fed Depdc5-LKO mice developed severe hepatic steatosis and inflammation. Pharmacological intervention with Torin 1 suppressed mTORC1 activity and remarkably ameliorated ethanol-induced hepatic steatosis and inflammation in both control and Depdc5-LKO mice. The pathological effect of sustained mTORC1 activity in ALD may be attributed to the suppression of peroxisome proliferator activated receptor α (PPARα), the master regulator of fatty acid oxidation in hepatocytes, because fenofibrate (PPARα agonist) treatment reverses ethanol-induced liver steatosis and inflammation in Depdc5-LKO mice. These findings provide novel insights into the in vivo role of hepatic DEPDC5 in the development of ALD.
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http://dx.doi.org/10.1038/s41419-021-03980-6DOI Listing
July 2021

Generalized optical design and optimization of multipass cells with independent circle patterns based on the Monte Carlo and Nelder-Mead simplex algorithms.

Opt Express 2021 Jun;29(13):20250-20261

In this paper, we propose an automatic approach to optimize the multipass cell (MPC) design with independent circle patterns. First, the Monte Carlo algorithm is performed to globally search for the characteristic values of the distance between two mirrors. Second, the Nelder-Mead simplex (NM) algorithm is applied to locally optimize the re-entry condition. In addition, we utilize the clustering method to select the independent circle patterns automatically. Three optimal MPCs with five, seven and nine independent circles are built and tested experimentally. We analyze the stability of the final point for the MPCs and optimize the quality of the output beam based on multi-ray tracing. This type of MPC shows the superior characteristics of compactness, high detection sensitivity, and affordability, has various applications, and can promote the development of portable gas sensors. The proposed approach is effective and efficient for automatically optimizing MPC design and can be further extended to versatile optical designs.
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http://dx.doi.org/10.1364/OE.429953DOI Listing
June 2021

sp. nov., a novel member of the class .

Int J Syst Evol Microbiol 2021 Jul;71(7)

Key Laboratory of Marine Ecosystem Dynamics, Ministry of Natural Resources & Second Institute of Oceanography, Ministry of Natural Resources, Hangzhou 310012, PR China.

A Gram-stain-positive, aerobic, chemo-organotrophic, rod-shaped, non-spore-forming strain, which produced convex, circular, pink-pigmented colonies, designated as DY32-46, was isolated from seawater collected from the Pacific Ocean. DY32-46 was found to grow at 20-40 °C (optimum, 30-35 °C), pH 6.0-8.0 (optimum, pH 6.5) and with 0-5 % (w/v) NaCl (optimum, 1-2 %). The results of chemotaxonomic analysis indicated that the respiratory quinone of DY32-46 was MK-9(H), and major fatty acids (>10 %) were C 8, summed feature 3 (C 7 and/or C 6), C and C 6. The polar lipids included diphosphatidylglycerol, phosphatidylglycerol, one unidentified aminophospholipid, three unidentified glycolipids, three unidentified phospholipids, one unidentified phosphoglycolipid and five unidentified lipids. The DNA G+C content of DY32-46 was 70.6 mol%. The results of phylogenetic analysis based on 16S rRNA gene sequences and genomic data indicated that DY32-46 should be assigned to the genus . ANI and DNA-DNA hybridization values between strain DY32-46 and type strains of species were 73.1-87.2 % and 20.2-32.4 %, respectively. Different phenotypic properties, together with genetic distinctiveness, demonstrated that strain DY32-46 was clearly distinct from recognized species of the genus . Therefore, DY32-46 represents a novel species within the genus , for which the name sp. nov is proposed. The type strain is DY32-46 (=MCCC 1K03476=KCTC 49091).
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http://dx.doi.org/10.1099/ijsem.0.004864DOI Listing
July 2021

Air Pollution, Genetic Factors and the Risk of Lung Cancer: A Prospective Study in the UK Biobank.

Am J Respir Crit Care Med 2021 Jul 12. Epub 2021 Jul 12.

Nanjing Medical University School of Public Health, 572407, Department of Epidemiology, Center for Global Health, Nanjing, China.

Both genetic and environmental factors contribute to lung cancer, but the degree to which air pollution modifies the impact of genetic susceptibility on lung cancer remains unknown. To investigate whether air pollution and genetic factors jointly contribute to incident lung cancer. We analyzed data from 455,974 participants (53% women) without previous cancer at baseline in the UK Biobank. The concentrations of particulate matter (PM, PM and PM), nitrogen dioxide (NO), and nitrogen oxides (NO) were estimated by land-use regression models, and the association between air pollutants and incident lung cancer was investigated using a Cox proportional hazard model. Furthermore, we constructed a polygenic risk score and evaluated whether air pollutants modified the effect of genetic susceptibility on the development of lung cancer. The results showed significant associations between the risk of lung cancer and PM (hazard ratio [HR]: 1.63, 95% confidence interval [CI]: 1.33-2.01; per 5 μg/m), PM (1.53, 1.20-1.96; per 10 μg/m), NO (1.10, 1.05-1.15; per 10 μg/m), and NO (1.13, 1.07-1.18; per 20 μg/m). There were additive interactions between air pollutants and the genetic risk. Compared with participants with low genetic risk and low air pollution, those with high air pollution and high genetic risk had the highest risk of lung cancer (PM: HR: 1.71, 95% CI:1.45-2.02; PM: 1.77, 1.50-2.10; NO: 1.77, 1.42-2.22; NO: 1.67, 1.43-1.95). Long-term exposure to air pollution may increase the risk of lung cancer, especially in those with high genetic risk.
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http://dx.doi.org/10.1164/rccm.202011-4063OCDOI Listing
July 2021

The role of CCR2 in prognosis of patients with endometrial cancer and tumor microenvironment remodeling.

Bioengineered 2021 Dec;12(1):3467-3484

Department of Obstetrics and Gynecology, The Affiliated Obstetrics and Gynecology Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu, China.

Tumor microenvironment (TME) plays a core role in the genesis and progress of endometrial carcinoma (EC). The immune system, a crucial element of TME, functions in various immune cells. In this paper, we have tried to evaluate the prognosis in EC patients by the status of TME. The ESTIMATE algorithm was implemented to computer the number of immune and stromal components in EC tissues from the Cancer Genome Atlas dataset. The CIBERSORT algorithm was employed to assess the proportion of tumor-infiltrating immune cells in EC tissues, which were quantified as Stromal score and Immune score. After the construction of protein-protein interaction network, cell-cell chemokine receptor 2 (CCR2) was identified as a potential predictive element for EC. Further analysis indicated that a higher expression of CCR2 in EC patients was correlated with a better prognosis and a prolonged disease-free survival. According to the transcript level of CCR2, samples were separated into low- and high-expression groups. Gene Set Enrichment Analysis unveiled that metabolism-related pathways were mostly abundant in groups with high-expression, the other one was primarily correlated to immune-related activities. We figured out that some immune cells were positively related to CCR2, suggesting that CCR2 might serve as the immune-dominant status of TME, which was verified by qRT-PCR and HPA analysis in transcriptome and protein level, respectively. Also, CCR2 showed high correlation with immune modulators and chemokine signaling pathway. Thus, the level of CCR2 might have a prognostic value for EC patients, which provides a novel insight for therapeutic strategies of EC.
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http://dx.doi.org/10.1080/21655979.2021.1947631DOI Listing
December 2021

Identification of Koumine as a Translocator Protein 18 kDa Positive Allosteric Modulator for the Treatment of Inflammatory and Neuropathic Pain.

Front Pharmacol 2021 24;12:692917. Epub 2021 Jun 24.

Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou, China.

Koumine is an alkaloid that displays notable activity against inflammatory and neuropathic pain, but its therapeutic target and molecular mechanism still need further study. Translocator protein 18 kDa (TSPO) is a vital therapeutic target for pain treatment, and recent research implies that there may be allostery in TSPO. Our previous competitive binding assay hint that koumine may function as a TSPO positive allosteric modulator (PAM). Here, for the first time, we report the pharmacological characterization of koumine as a TSPO PAM. The results imply that koumine might be a high-affinity ligand of TSPO and that it likely acts as a PAM since it could delay the dissociation of H-PK11195 from TSPO. Importantly, the allostery was retained , as koumine augmented Ro5-4864-mediated analgesic and anti-inflammatory effects in several acute and chronic inflammatory and neuropathic pain models. Moreover, the positive allosteric modulatory effect of koumine on TSPO was further demonstrated in cell proliferation assays in T98G human glioblastoma cells. In summary, we have identified and characterized koumine as a TSPO PAM for the treatment of inflammatory and neuropathic pain. Our data lay a solid foundation for the use of the clinical candidate koumine to treat inflammatory and neuropathic pain, further demonstrate the allostery in TSPO, and provide the first proof of principle that TSPO PAM may be a novel avenue for the discovery of analgesics.
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http://dx.doi.org/10.3389/fphar.2021.692917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264504PMC
June 2021

Empagliflozin in Patients With Heart Failure: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Front Cardiovasc Med 2021 22;8:683281. Epub 2021 Jun 22.

National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

The purpose of the study is to evaluate the effect of empagliflozin in patients with heart failure (HF). We performed a systematic search of PubMed, EMBASE, and the Cochrane Library database through January 20, 2021. Randomized controlled trials (RCTs) were included that compared empagliflozin and placebo in patients with HF. Dichotomous variables were expressed as risk ratios (RRs) with 95% confidence intervals (CIs). Continuous variables were calculated and expressed as mean differences (MD) and standard deviation (SD). Meta-analysis was conducted using a random-effects model on outcomes with high heterogeneity. Seven studies were included in our meta-analysis ( = 5,150). Significant differences were observed in a composite of cardiovascular death or hospitalization for worsening heart failure [RR: 0.77 (95% CI 0.68-0.87); = 18%; < 0.0001), hospitalization for worsening heart failure [RR: 0.71 (95% CI 0.61-0.82); = 0%; < 0.00001], changes in Kansas City Cardiomyopathy Questionnaire (KCCQ) score [MD: 1.70 (95% CI 1.67-1.73); = 0%; < 0.00001], and changes in body weight [MD: -1.43 (95% CI -2.15 to -0.72); = 84%; < 0.0001) from baseline. However, empagliflozin did not show a better change in the 6-min walk test (6MWT) [MD: 34.06 (95% CI -29.75-97.88); = 97%; = 0.30] or NT-proBNP [MD: -98.36 (95% CI, -225.83-29.11); = 68%; = 0.13] from baseline. The findings suggest that empagliflozin was effective in reducing a composite of cardiovascular death or hospitalization for worsening heart failure. Further well-designed RCTs are needed to evaluate the long-term effect of empagliflozin in patients with HF. CRD42021231712.
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http://dx.doi.org/10.3389/fcvm.2021.683281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257947PMC
June 2021

Early-life inflammation promotes depressive symptoms in adolescence via microglial engulfment of dendritic spines.

Neuron 2021 Jun 26. Epub 2021 Jun 26.

Department of Anesthesiology, The First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at the Microscale, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230036, China. Electronic address:

Early-life inflammation increases the risk for depression in later life. Here, we demonstrate how early-life inflammation causes adolescent depressive-like symptoms: by altering the long-term neuronal spine engulfment capacity of microglia. For mice exposed to lipopolysaccharide (LPS)-induced inflammation via the Toll-like receptor 4/NF-κB signaling pathway at postnatal day (P) 14, ongoing longitudinal imaging of the living brain revealed that later stress (delivered during adolescence on P45) increases the extent of microglial engulfment around anterior cingulate cortex (ACC) glutamatergic neuronal (ACC) spines. When the ACC microglia of LPS-treated mice were deleted or chemically inhibited, the mice did not exhibit depressive-like behaviors during adolescence. Moreover, we show that the fractalkine receptor CX3CR1 mediates stress-induced engulfment of ACC neuronal spines. Together, our findings establish that early-life inflammation causes dysregulation of microglial engulfment capacity, which encodes long-lasting maladaptation of ACC neurons to stress, thus promoting development of depression-like symptoms during adolescence.
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http://dx.doi.org/10.1016/j.neuron.2021.06.012DOI Listing
June 2021

Association of fish consumption with risk of all-cause and cardiovascular disease mortality: an 11-year follow-up of the Guangzhou Biobank Cohort Study.

Eur J Clin Nutr 2021 Jul 6. Epub 2021 Jul 6.

School of Public Health, Sun Yat-sen University, Guangzhou, China.

Background: Whether fish consumption is associated with all-cause, cardiovascular (CVD), ischemic heart disease (IHD) and stroke mortality remains inconclusive. We examined the association of fish consumption with all-cause, cardiovascular (CVD), ischemic heart disease (IHD) and stroke mortality in older men and women in south China.

Methods: A total of 18,215 participants including men and women without CVD at baseline (2003-2006) from Guangzhou Biobank Cohort Study (GBCS) were included and followed up till December 2017. Deaths were identified through record linkage with the Death Registry. Information on fish consumption was obtained using a food frequency questionnaire.

Results: During an average follow-up of 11.4 (standard deviation = 2.1) years, 2,697 deaths occurred, including 917 total CVD, 397 IHD and 374 stroke deaths. After adjusting for potential confounders, compared with fish consumption of 0-3 servings/week (i.e., 0-21 g/day, one serving = 50 g), consumption of 4-6 servings/week (29-43 g/day) showed significantly lower risks of all-cause and CVD mortality (hazards ratio (HR) and 95% confidence interval (CI): 0.85 (0.76, 0.95) and 0.77 (0.64, 0.93), respectively), but the reduced risk of IHD mortality (HR (95% CI): 0.80 (0.60, 1.07)) was not significant. Consumption of 7-10 servings/week or higher showed no association with all-cause, CVD, IHD, and stroke mortality.

Conclusions: Moderate fish consumption of 4-6 servings/week (29-43 g/day) was associated with lower all-cause and CVD mortality risk. Our findings support the current general advice on regular fish consumption also in middle-aged and older adults.
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http://dx.doi.org/10.1038/s41430-021-00968-5DOI Listing
July 2021

Association of healthy lifestyle score with all-cause mortality and life expectancy: a city-wide prospective cohort study of cancer survivors.

BMC Med 2021 Jul 7;19(1):158. Epub 2021 Jul 7.

School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China.

Background: Adherence to a healthy lifestyle could reduce the cancer mortality in the western population. We conducted a city-wide prospective study in China investigating the association of a healthy lifestyle score with all-cause mortality and the life expectancy in cancer survivors.

Methods: This prospective cohort study included 46,120 surviving patients who were firstly diagnosed with cancer in Guangzhou. Five low-risk lifestyle factors including never smoking, never alcohol use, regular physical activity (≥ 2 h/week), sufficient sleep (≥ 6 h/day), and normal or high BMI (≥ 18.5 kg/m) were assessed and a lifestyle score (0-5, a higher score indicates healthier lifestyle) was generated. Hazard ratios (HRs) of all-cause mortality and the life expectancy by levels of the lifestyle scores were estimated.

Results: Of 46,120 cancer survivors registered from 2010 to 2017, during an average follow-up of 4.3 years (200,285 person-years), 15,209 deaths were recorded. Adjusted HRs for mortality in cancer survivors with lifestyle score of 0-2, versus 5, were 2.59 (95% confidence interval (CI): 2.03-3.30) in women, 1.91 (95%CI 1.77-2.05) in men, 2.28 (95%CI 2.03-2.55) in those aged <65 years, and 1.90 (95%CI 1.75, 2.05) in those aged ≥ 65 years. Life expectancy at age 55 for those with a score of 0-2 and 5 was 53.4 and 57.1 months, respectively. We also found that cancer survivors with healthy lifestyle scores of 5 showed 59.9 months of life expectancy on average, which was longer than those with a score of 0-2.

Conclusion: Adopting a healthy lifestyle was associated with a substantially lower risk of all-cause mortality and longer life expectancy in cancer survivors. Our findings should be useful for health education and health promotion in primary care and clinical practice.
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http://dx.doi.org/10.1186/s12916-021-02024-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261938PMC
July 2021

Case Report: Pink Urine Syndrome Following Exposure to Propofol: A Rare, Impressive but Benign Complication.

Front Pharmacol 2021 15;12:686619. Epub 2021 Jun 15.

Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China.

Drug-induced changes in urine color induced by drugs may have clinical significance. Pink urine syndrome (PUS), which has been associated with urinary uric acid (UA) disorders, is most frequently reported in patients with morbid obesity undergoing gastric bypass surgery and/or from propofol anesthesia use in those who potentially have preexisting UA metabolism disorders. However, PUS has rarely occurred following exposure to propofol in non-obese patients, and literature on long-term follow-up after PUS is scarce. We report a case of PUS induced by propofol in a previously healthy non-obese woman after undergoing thoracoscopic wedge resection of pulmonary nodules under general anesthesia using propofol. The patient suddenly developed pink urine 4 h after surgery. A pink sediment rapidly precipitated at the bottom of the test tube following centrifugation of the urine. Amorphous, colorless UA-like crystals were identified under a polarizing microscope. The diagnosis of PUS was confirmed by examining the urinary UA concentration. The patient recovered and as followed-up for 1 month, during which she did not experience any urinary complications. To our knowledge, this is the first report to describe in detail a case of PUS caused by propofol in a non-obese patient with follow-up. PUS is usually benign and can resolve by rapidly on administering lactated Ringer's solution; however, the potential risk of urinary complications, particularly UA lithiasis, should be fully realized.
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http://dx.doi.org/10.3389/fphar.2021.686619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241095PMC
June 2021

Can Carbon Nanotube Transistors Be Scaled Down to the Sub-5 nm Gate Length?

ACS Appl Mater Interfaces 2021 Jul 2;13(27):31957-31967. Epub 2021 Jul 2.

Key Laboratory for the Physics and Chemistry of Nanodevices and Department of Electronics and Center for Carbon-based Electronics, Peking University, Beijing 100871, P. R. China.

Single-walled carbon nanotubes (CNTs) have been considered as a promising semiconductor to construct transistors and integrated circuits in the future owing to their ultrathin channel thickness and ultrahigh injection velocity. Although a 5 nm gate-length CNT field-effect transistor (FET) has already been experimentally fabricated and demonstrates excellent device performance, the potential or constraint factors on performance have not been explored or revealed. Based on the benchmark of the device performance between the experimental and simulated 5 nm gate-length CNT FETs, we use the first-principles quantum transport approach to explore the performance limit of CNT FETs based on the gate-all-around (GAA) device geometry for the first time. It is found that the GAA CNT FETs can fulfill the ITRS 2028 high-performance target in the 2 nm gate-length node in terms of the on-state current, delay time, and power consumption. We also find that the energy-delay product of the CNT FETs is superior to those of the high-performance 2D materials and Si Fin FETs at the sub-5 nm gate length due to its unique electrical property. Though theoretically the gate length of CNT FETs can be potentially scaled to 2 nm, considering the tradeoff between the performance and power consumption, 5 nm is the ultimate scaled limit.
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http://dx.doi.org/10.1021/acsami.1c05229DOI Listing
July 2021

Plasma Sphingolipid Profile in Association with Incident Metabolic Syndrome in a Chinese Population-Based Cohort Study.

Nutrients 2021 Jun 30;13(7). Epub 2021 Jun 30.

Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

Although bioactive sphingolipids have been shown to regulate cardiometabolic homeostasis and inflammatory signaling pathways in rodents, population-based longitudinal studies of relationships between sphingolipids and onset of metabolic syndrome (MetS) are sparse. We aimed to determine associations of circulating sphingolipids with inflammatory markers, adipokines, and incidence of MetS. Among 1242 Chinese people aged 50-70 years who completed the 6-year resurvey, 76 baseline plasma sphingolipids were quantified by high-throughput liquid chromatography-tandem mass spectrometry. There were 431 incident MetS cases at 6-year revisit. After multivariable adjustment including lifestyle characteristics and BMI, 21 sphingolipids mainly from ceramide and hydroxysphingomyelin subclasses were significantly associated with incident MetS. Meanwhile, the baseline ceramide score was positively associated (RR = 1.31; 95% CI 1.05, 1.63; = 0.010) and the hydroxysphingomyelin score was inversely associated (RR = 0.60; 95% CI 0.45, 0.79; < 0.001) with incident MetS. When further controlling for clinical lipids, both associations were attenuated but remained significant. Comparing extreme quartiles, RRs (95% CIs) of MetS risk were 1.34 (95% CI 1.06, 1.70; = 0.010) for ceramide score and 0.71 (95% CI 0.51, 0.97; = 0.018) for hydroxysphingomyelin score, respectively. Furthermore, a stronger association between ceramide score and incidence of MetS was evidenced in those having higher inflammation levels (RR 1.57; 95% CI 1.16, 2.12; = 0.004). Our data suggested that elevated ceramide concentrations were associated with a higher MetS risk, whereas raised hydroxysphingomyelin levels were associated with a lower MetS risk beyond traditional clinical lipids.
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http://dx.doi.org/10.3390/nu13072263DOI Listing
June 2021

Analytical Modeling of a Doubly Clamped Flexible Piezoelectric Energy Harvester with Axial Excitation and Its Experimental Characterization.

Sensors (Basel) 2021 Jun 3;21(11). Epub 2021 Jun 3.

Institute of Intelligent Manufacturing and Control, Wuhan University of Technology, Wuhan 430063, China.

With the rapid development of wearable electronics, novel power solutions are required to adapt to flexible surfaces for widespread applications, thus flexible energy harvesters have been extensively studied for their flexibility and stretchability. However, poor power output and insufficient sensitivity to environmental changes limit its widespread application in engineering practice. A doubly clamped flexible piezoelectric energy harvester (FPEH) with axial excitation is therefore proposed for higher power output in a low-frequency vibration environment. Combining the Euler-Bernoulli beam theory and the D'Alembert principle, the differential dynamic equation of the doubly clamped energy harvester is derived, in which the excitation mode of axial load with pre-deformation is considered. A numerical solution of voltage amplitude and average power is obtained using the Rayleigh-Ritz method. Output power of 22.5 μW at 27.1 Hz, with the optimal load resistance being 1 MΩ, is determined by the frequency sweeping analysis. In order to power electronic devices, the converted alternating electric energy should be rectified into direct current energy. By connecting to the MDA2500 standard rectified electric bridge, a rectified DC output voltage across the 1 MΩ load resistor is characterized to be 2.39 V. For further validation of the mechanical-electrical dynamical model of the doubly clamped flexible piezoelectric energy harvester, its output performances, including both its frequency response and resistance load matching performances, are experimentally characterized. From the experimental results, the maximum output power is 1.38 μW, with a load resistance of 5.7 MΩ at 27 Hz, and the rectified DC output voltage reaches 1.84 V, which shows coincidence with simulation results and is proved to be sufficient for powering LED electronics.
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http://dx.doi.org/10.3390/s21113861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199891PMC
June 2021

Associations between Adherence to Four A Priori Dietary Indexes and Cardiometabolic Risk Factors among Hyperlipidemic Patients.

Nutrients 2021 Jun 24;13(7). Epub 2021 Jun 24.

School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518106, China.

Little is known about which currently available a priori dietary indexes provide best guidance for reducing cardiometabolic risk factors (CMRF) among hyperlipidemic patients. This study was designed to compare the associations between four a priori dietary indexes, including Diet Balance Index (DBI-16), Chinese Healthy Eating Index (CHEI), Mediterranean Diet Score (MDS) and Dietary Approaches to Stop Hypertension (DASH) and CMRF among hyperlipidemic patients. A total of 269 participants were enrolled into the cross-sectional study. DBI-16, CHEI, MDS, and DASH scores were calculated using established methods. CMRF was measured using standard methods. DBI-total scores (DBI-TS) were inversely associated with triglyceride concentrations and TC:HDL-C ratio, and positively associated with HDL-C and ApoA1 concentrations (all < 0.05), while the results for DBI-low bound scores (DBI-LBS) were opposite. DBI-high bound scores (DBI-HBS) and DASH scores were positively and inversely associated with glucose concentrations, respectively (both < 0.05). Higher diet quality distance (DQD) was positively associated with higher TC, LDL-C and ApoB concentrations, and TC:HDL-C and LDL-C:HDL-C ratios, and lower HDL-C and ApoA1 concentrations and ApoA1:ApoB ratio (all < 0.05). CHEI scores were inversely associated with triglyceride concentrations ( = 0.036). None of the dietary indexes was associated with blood pressures. DBI-16 provided most comprehensive evaluations of the overall diet quality and balance for optimizing cardiometabolic health among hyperlipidemic individuals.
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http://dx.doi.org/10.3390/nu13072179DOI Listing
June 2021

Genetic diversity and evolutionary patterns of Rodin.

Ecol Evol 2021 Jun 7;11(12):7917-7926. Epub 2021 May 7.

State Key Laboratory of Cotton Biology Institute of Cotton Research Chinese Academy of Agricultural Sciences Anyang China.

Rodin (TKS) is an important potential alternative source of natural inulin and rubber production, which has great significance for the production of industrial products. In this study, we sequenced 58 wild TKS individuals collected from four different geography regions worldwide to elucidate the population structure, genetic diversity, and the patterns of evolution. Also, the first flowering time, crown diameter, morphological characteristics of leaf, and scape of all TKS individuals were measured and evaluated statistically. Phylogenetic analysis based on SNPs and cluster analysis based on agronomic traits showed that all 58 TKS individuals could be roughly divided into three distinct groups: (a) Zhaosu County in Xinjiang (population AB, including a few individuals from population C and D); (b) Tekes County in Xinjiang (population C); and (c) Tuzkol lake in Kazakhstan (population D). Population D exhibited a closer genetic relationship with population C compared with population AB. Genetic diversity analysis further revealed that population expansion from C and D to AB occurred, as well as gene flow between them. Additionally, some natural selection regions were identified in AB population. Function annotation of candidate genes identified in these regions revealed that they mainly participated in biological regulation processes, such as transporter activity, structural molecule activity, and molecular function regulator. We speculated that the genes identified in selective sweep regions may contribute to TKS adaptation to the Yili River Valley of Xinjiang. In general, this study provides new insights in clarifying population structure and genetic diversity analysis of TKS using SNP molecular markers and agronomic traits.
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http://dx.doi.org/10.1002/ece3.7622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216896PMC
June 2021

New insight into the adsorption mechanism of PCP by humic substances with different degrees of humification in the presence of Cr(VI).

Chemosphere 2021 Jun 22;284:131223. Epub 2021 Jun 22.

Beijing Key Laboratory of Water Resources and Environmental Engineering, School of Water Resources and Environment, China University of Geosciences, Beijing, 100083, China.

Humic substances (HSs) have great retention effects on pentachlorophenol (PCP) migration in subsurface environment, but the adsorption mechanism of PCP by HSs with various aromatic/aliphatic moieties and acidic functional groups in the presence of Cr(VI) is still unclear. In this study, the adsorption mechanism of PCP by undissolved humic acid (HA) and humin (HM) extracted from peat, black soil, lignite and coal was investigated under the presence of Cr(VI). According to the results, HA samples had much lower adsorption capacity for hydrophobic PCP than HM samples due to their higher contents of hydrophilic polar oxygen-containing functional groups. In respect to PCP adsorption mechanism, the molecular unsaturation of HSs associated with humification degree was found to be the determinant instead of polarity. Notably, after reacting with Cr(VI), significant decreasing of PCP adsorption quantities occurred on HSs extracted from lignite and coal with higher degrees of unsaturation (H/C < 0.64), while HSs extracted from peat and black soil with lower degrees of unsaturation (H/C > 0.83) kept almost unchanged, which can be attributed to the much higher reactivity of aromatic domains of HSs for Cr(VI) reduction compared with aliphatic moieties. This indicated that the adsorption mechanism of PCP by HSs with higher and lower degrees of unsaturation might be respectively driven by π-π interaction and hydrophobic interaction. This study highlighted the diverse adsorption mechanisms of PCP on HSs with different degrees of humification, and emphasized the coexisting Cr(VI) only have significant effect on PCP adsorption by HSs with higher humification degrees instead of the lower ones.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131223DOI Listing
June 2021

Nose-to-brain delivery of borneol modified tanshinone IIA nanoparticles in prevention of cerebral ischemia/reperfusion injury.

Drug Deliv 2021 Dec;28(1):1363-1375

Institute of Interdisciplinary Integrative Medicine Research, Murad Research Center for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China.

Targeted treatment of cerebral ischemia/reperfusion injury (CIRI) remains a problem due to the difficulty in drug delivery across the blood-brain barrier (BBB). In this study, we developed Bo-TSA-NP, a novel tanshinone IIA (TSA) loaded nanoparticles modified by borneol, which has long been proved with the ability to enhance other drugs' transport across the BBB. The Bo-TSA-NP, with a particle size of about 160 nm, drug loading of 3.6%, showed sustained release and P-glycoprotein (P-gp) inhibition property. It demonstrated a significantly higher uptake by 16HBE cells through the clathrin/caveolae-mediated endocytosis and micropinocytosis. Following intranasal (IN) administration, Bo-TSA-NP significantly improved the preventive effect on a rat model of CIRI with improved neurological scores, decreased cerebral infarction areas and a reduced content of malondialdehyde (MDA) and increased activity of superoxide dismutase (SOD) in rat brain. In conclusion, these results indicate that Bo-TSA-NP is a promising nose-to-brain delivery system that can enhance the prevention effect of TSA on CIRI.
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http://dx.doi.org/10.1080/10717544.2021.1943058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245080PMC
December 2021

Subjective Cognitive Decline May Be Associated With Post-operative Delirium in Patients Undergoing Total Hip Replacement: The PNDABLE Study.

Front Aging Neurosci 2021 11;13:680672. Epub 2021 Jun 11.

Department of Anesthesiology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, China.

Subjective cognitive decline (SCD) is associated with an increased risk of clinical cognitive disorders. Post-operative delirium (POD) is a common complication after total hip replacement. We aimed to investigate the relationship between SCD and POD in patients undergoing total hip replacement. Our study recruited 214 cognitively intact individuals from the Perioperative Neurocognitive Disorder And Biomarker Lifestyle (PNDABLE) study in the final analysis. SCD was diagnosed with Subjective Cognitive Decline Scale (SCDS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). The incidence of POD was evaluated by using Confusion Assessment Method (CAM), and POD severity was measured by using the Memorial Delirium Assessment Scale (MDAS). Preoperative cerebrospinal fluid (CSF) Aβ40, Aβ42, T-tau, and P-tau levels were measured by enzyme-linked immune-sorbent assay (ELISA). Overall, the incidence of POD was 26.64% (57/214), including 32.43% (36/111) in the SCD group and 20.39% (21/103) in the NC group. With the increase of age, the incidence of POD in all age groups increased ( < 0.05). Logistic regression analysis showed that after adjusting for SCD, Aβ42, Aβ40, P-tau, and T-tau, SCD (OR 2.32, CI 1.18-4.55, = 0.01) and the increased CSF level of P-tau (OR 1.04, CI 1.01-1.06, < 0.001) were risk factors for POD, while the level of aβ42 (OR 0.99, CI 0.99-1.00, < 0.001) was a protective factor for POD. SCD is one of the preoperative risk factors for POD. This study was registered at China Clinical Trial Registry (Chictr200033439).
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http://dx.doi.org/10.3389/fnagi.2021.680672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225929PMC
June 2021

Philippines braces for the typhoon season amidst COVID-19.

Lancet Reg Health West Pac 2020 Aug 3;1:100003. Epub 2020 Aug 3.

Faculty of Pharmacy, University of Ibadan, Ibadan, Nigeria.

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http://dx.doi.org/10.1016/j.lanwpc.2020.100003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398084PMC
August 2020

Deep learning-based automated left ventricular ejection fraction assessment using 2D echocardiography.

Am J Physiol Heart Circ Physiol 2021 Jun 25. Epub 2021 Jun 25.

Division of Cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Laboratory of Cardiac Imaging and 3D Printing, Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, Sha Tin, Hong Kong SAR, China.

Background: Deep-learning (DL) has been applied for automatic left ventricle (LV) ejection fraction (EF) measurement, but the diagnostic performance was rarely evaluated for various phenotypes of heart disease. This study aims to evaluate a new DL algorithm for automated LVEF measurement using two-dimensional echocardiography (2DE) images collected from 3 centers. The impact of 3 ultrasound machines and 3 phenotypes of heart diseases on the automatic LVEF measurement was evaluated.

Methods And Results: Using 36890 frames of 2DE from 340 patients, we developed a DL algorithm based on U-Net (DPS-Net) and the biplane Simpson's method was applied for LVEF calculation. Results showed a high performance in LV segmentation and LVEF measurement across phenotypes and echo systems by using DPS-Net. Good performance was obtained for LV segmentation when DPS-Net was tested on the CAMUS dataset (Dice coefficient of 0.932 and 0.928 for ED and ES). Better performance of LV segmentation in study-wise evaluation was observed by comparing the DPS-Net v2 to the EchoNet-dynamic algorithm (p = 0.008). DPS-Net was associated with high correlations and good agreements for the LVEF measurement. High diagnostic performance was obtained that the area under receiver operator characteristic curve was 0.974, 0.948, 0.968 and 0.972 for normal hearts and disease phenotypes including atrial fibrillation, hypertrophic cardiomyopathy, dilated cardiomyopathy, respectively.

Conclusion: High performance was obtained by using DPS-Net in LV detection and LVEF measurement for heart failure with several phenotypes. High performance was observed in a large-scale dataset, suggesting that the DPS-Net was highly adaptive across different echocardiographic systems.
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http://dx.doi.org/10.1152/ajpheart.00416.2020DOI Listing
June 2021

Intraoperative Oxygen Concentration and Postoperative Delirium After Laparoscopic Gastric and Colorectal Malignancies Surgery: A Randomized, Double-Blind, Controlled Trial.

Clin Interv Aging 2021 15;16:1085-1093. Epub 2021 Jun 15.

Department of Anesthesiology, Qingdao Municipal Hospital Affiliated to Qingdao University, Qingdao, People's Republic of China.

Purpose: Postoperative delirium (POD) is common in elderly patients undergoing laparoscopic surgery for gastric and colorectal malignancies. POD may be affected by different fraction of inspired oxygen (FiO). The purpose of this study was to compare the effects of different FiO on POD.

Patients And Methods: A randomized, double-blind controlled trial was performed in Qingdao Municipal Hospital Affiliated to Qingdao University. A total of 662 patients aged 65 to 85 years old underwent isolated laparoscopic radical gastrectomy, radical resection of colon cancer, or radical resection of rectal cancer only. A random number table method was used to divide the patients into two groups: 40% FiO (group A) and 80% FiO (group B). The primary endpoint was the incidence of POD, which was assessed by the Confusion Assessment Method (CAM) twice daily during the first 7 postoperative days, and POD severity was measured by the Memorial Delirium Assessment Scale (MDAS). The secondary endpoints were the intraoperative regional cerebral oxygen saturation (rSO), Bispectral (BIS) index, invasive arterial blood pressure (IABP), oxygen saturation (SpO), end-tidal carbon dioxide partial pressure (PCO), the number of atelectasis cases and visual analogue scale (VAS) scores on days 1-7 after surgery.

Results: The incidence of POD was 19.37% (122/630), including 20.38% (64/314) in group A and 18.35% (58/316) in group B. No statistical significance was found in the incidence of POD between the two groups ( > 0.05); compared with group B, SpO, rSO and PaO decreased at T to T time point ( < 0.01), and the incidence of postoperative atelectasis decreased ( < 0.05) in group A.

Conclusion: The incidence of POD was not significantly affected by different FiO and the incidence of postoperative atelectasis was decreased at low FiO.
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http://dx.doi.org/10.2147/CIA.S311190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214551PMC
July 2021