Publications by authors named "Lijuan Xu"

161 Publications

Moderating effect of work-related social support on the relationship between role conflicts and job satisfaction among female nurses pursuing a further degree in China.

Int J Nurs Pract 2021 Sep 12:e13014. Epub 2021 Sep 12.

Medicine College of Lishui University, Lishui, China.

Purpose: This study aimed to determine the moderating effect of work-related social support on the relationship between work-family-school role conflicts and job satisfaction among female registered nurses pursuing further degrees in China.

Methods: The study had a cross-sectional correlational design. Convenience sampling was applied to recruit participants from eight hospitals in China from January to August 2017. SPSS software and the PROCESS macro were used to conduct the data analyses in the present study.

Results: A total of 320 nurses were included in the present study. Work-family-school role conflicts were negatively correlated with job satisfaction (r = -0.21, P < 0.001). Work-related social support was a significant moderator (interaction effect: β = 0.22, P = 0.039) on the relationship between work-family-school role conflicts and job satisfaction.

Conclusions: The study revealed that when nurses perceived that they received a low or moderate level of social support in the workplace that strengthened the relationship between work-family-school role conflicts and job satisfaction. Hospital administrators should implement school- and family-friendly policies that increase the social support provided to nurses pursuing further degrees to balance their responsibilities of work, family and school and to improve their job satisfaction.
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http://dx.doi.org/10.1111/ijn.13014DOI Listing
September 2021

Blocking of Birc3/TLR4/Myd88 signaling protects carbapenem-resistant klebsiella pneumoniae in a mouse model of infection.

Transpl Immunol 2021 Sep 6:101464. Epub 2021 Sep 6.

Department of Clinical Laboratory, The Second People's Hospital of Lanzhou City, Lanzhou 730046, China.

Background: Klebsiella pneumonia (KP) and carbapenem-resistant Klebsiella pneumonia (CRKP) lung infections significantly increase the morbidity and mortality of pneumonia. Recent studies have shown that baculoviral IAP repeat-containing 3 (Birc3) plays an important role in the prevention and treatment of pneumonia. However, the role of Birc3 in CRKP-induced pneumonia has not been widely reported.

Methods: In vivo, we successfully established a mouse model of pneumonia induced by KP and CRKP. In vitro, we established a macrophage model treated with KP and CRKP. The phagocytosis of macrophages treated with CRKP was measured by Flow cytometry and coated plate counting. STRING and Co-IP assays were used to predict and verify the relationship between Birc3 and toll-like receptor 4 (TLR4) or myeloid differentiation factor 88 (Myd88). HE staining was used to detect the lung pathological changes of anti-Birc3 IgG inhibited CRKP-induced inflammatory cells. The levels of inflammatory factors and proteins were detected by ELISA and Western blot, respectively.

Results: The phagocytic ability of macrophages was reduced, and the cytokine storm was enhanced in CRKP treated Raw264.7 cells. Macrophages treated with CRKP impaired phagocytosis. Birc3 could interact with TLR4 and MyD88. Anti-Birc3 IgG inhibited CRKP-induced inflammatory cell lung infiltration. In addition, mice treated with anti-Birc3 IgG improved the CRKP-induced inflammatory cell lung infiltration, bacterial spread, and cytokine storm by inhibiting the Birc3/TLR4/Myd88 signaling pathway.

Conclusion: The results suggest that Birc3 may serve as a target for the treatment of bacterial infection and lung inflammation in CRKP-induced pneumonia.
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http://dx.doi.org/10.1016/j.trim.2021.101464DOI Listing
September 2021

Containing the Transmission of COVID-19: A Modeling Study in 160 Countries.

Front Med (Lausanne) 2021 18;8:701836. Epub 2021 Aug 18.

Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China.

It is much valuable to evaluate the comparative effectiveness of the coronavirus disease 2019 (COVID-19) prevention and control in the non-pharmacological intervention phase of the pandemic across countries and identify useful experiences that could be generalized worldwide. In this study, we developed a susceptible-exposure-infectious-asymptomatic-removed (SEIAR) model to fit the daily reported COVID-19 cases in 160 countries. The time-varying reproduction number ( ) that was estimated through fitting the mathematical model was adopted to quantify the transmissibility. We defined a synthetic index ( ) based on the value of to reflect the national capability to control COVID-19. The goodness-of-fit tests showed that the SEIAR model fitted the data of the 160 countries well. At the beginning of the epidemic, the values of of countries in the European region were generally higher than those in other regions. Among the 160 countries included in the study, all European countries had the ability to control the COVID-19 epidemic. The Western Pacific Region did best in continuous control of the epidemic, with a total of 73.76% of countries that can continuously control the COVID-19 epidemic, while only 43.63% of the countries in the European Region continuously controlled the epidemic, followed by the Region of Americas with 52.53% of countries, the Southeast Asian Region with 48% of countries, the African Region with 46.81% of countries, and the Eastern Mediterranean Region with 40.48% of countries. Large variations in controlling the COVID-19 epidemic existed across countries. The world could benefit from the experience of some countries that demonstrated the highest containment capabilities.
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http://dx.doi.org/10.3389/fmed.2021.701836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416347PMC
August 2021

Psychometric evaluation of Nurse Professional Competence Scale-Short-form Chinese language version among nursing graduate students.

Nurs Open 2021 Sep 1. Epub 2021 Sep 1.

Department of Caring Science, Faculty of Health and Occupational Studies, University of Gävle, Gävle, Sweden.

Aim: The aim of the study was to determine the psychometric properties, construct validity and internal consistency of the Chinese language version of the Nurse Professional Competence scale short form.

Design: A methodological design was used.

Methods: Questionnaire data from 260 nursing students nearing graduation from 2 universities in China were analysed using confirmatory factor analysis, known-group validity and internal consistency.

Results: The confirmatory factor analysis revealed that the model was acceptable, and the analyses for known-group validity revealed statistically significant differences in all factors and the total scale of the Nurse Professional Competence scale short form. Internal consistency revealed that Cronbach's alpha values exceeded 0.70 for all factors and the total scale. The Chinese language version of the Nurse Professional Competence scale short form has acceptable construct validity and good internal consistency.
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http://dx.doi.org/10.1002/nop2.1036DOI Listing
September 2021

Follicular helper and follicular regulatory T cell subset imbalance is associated with higher activated B cells and abnormal autoantibody production in primary anti-phospholipid syndrome patients.

Clin Exp Immunol 2021 Jul 26. Epub 2021 Jul 26.

Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.

Primary anti-phospholipid antibody syndrome (pAPS) is a multi-organ autoimmune disease, and autoantibodies are involved in its pathogenesis. Follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr) are critical for B cell maturation and antibody production, but their roles in pAPS remain unknown. We enrolled 32 pAPS patients and 23 healthy controls (HCs) and comprehensively analyzed circulating Tfh and Tfr, as well as their subsets, using flow cytometry. Clinical data including autoantibody levels were collected and their correlations with Tfh and Tfr subsets were analyzed. In addition, correlation analyses between B cell functional subsets and Tfh and Tfr were performed. Changes and potential effects of serum cytokines on Tfr and Tfh were further explored. We found the circulating Tfr was significantly decreased while Tfh and Tfh/Tfr ratios were increased in pAPS patients. Tfh2, inducible T cell co-stimulator (ICOS)  programmed cell death 1 (PD-1)  Tfh and Ki-67  Tfh percentages were elevated, while CD45RA forkhead box protein 3 (FoxP3) , Helios , T cell immunoglobulin and ITIM (TIGIT)  and Ki-67  Tfr percentages were decreased in pAPS patients. New memory B cells and plasmablasts were increased and altered B cell subsets and serum autoantibodies were positively correlated with Tfh, Tfh2, ICOS PD-1  Tfh cells and negatively associated with Tfr, CD45RA FoxP3 Tfr and Helios  Tfr cells. In addition, pAPS with LA/aCL/β2GPI autoantibodies showed lower functional Tfr subsets and higher activated Tfh subsets. Serum interleukin (IL)-4, IL-21, IL-12 and transforming growth factor (TGF)-β1 were up-regulated and associated with Tfh and Tfr subset changes. Our study demonstrates that imbalance of circulating Tfr and Tfh, as well as their functional subsets, is associated with abnormal autoantibody levels in pAPS, which may contribute to the pathogenesis of pAPS.
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http://dx.doi.org/10.1111/cei.13647DOI Listing
July 2021

Predefined-time synchronization of competitive neural networks.

Neural Netw 2021 Oct 7;142:492-499. Epub 2021 Jul 7.

Shandong Provincial Key Laboratory of Computer Networks, Shandong Computer Science Center(National Supercomputer Center in Jinan), Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, China. Electronic address:

In this paper, the predefined-time synchronization of competitive neural networks (CNNs) is researched based on two different predefined-time stability theorems. In view of the bilayer structure of CNNs, we design two bilayer predefined-time controllers. The first controller utilizes sign function, while the second controller utilizes exponential function and Lyapunov function. In these two controllers, the predefined time is set as a controller parameter, and it can be an arbitrary positive constant. Under these two controllers, the considered CNNs can achieve synchronization within the predefined time regardless of the initial values. A specific example is presented to validate the theoretical results.
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http://dx.doi.org/10.1016/j.neunet.2021.06.026DOI Listing
October 2021

Circulating CD4  FoxP3  CXCR5  CXCR3  PD-1 cells are elevated in active rheumatoid arthritis and reflect the severity of the disease.

Int J Rheum Dis 2021 Aug 6;24(8):1032-1039. Epub 2021 Jul 6.

Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.

Objective: To examine the expression and clinical significance of circulating CD4  FoxP3  CXCR5  CXCR3  PD-1 cells in rheumatoid arthritis (RA).

Methods: CD4  FoxP3  CXCR5  CXCR3  PD-1 cells in peripheral blood of 35 patients with active RA, 17 with RA in stable remission, and 24 healthy controls were analyzed by flow cytometry. Serum IgG and circulating plasmablast percentages were measured and correlations with CD4  FoxP3  CXCR5  CXCR3  PD-1 cells were systematically analyzed. Disease Activity Scale 28 (DAS28) scores were also calculated and correlation analysis with CD4  FoxP3  CXCR5  CXCR3  PD-1 cells was conducted. The levels of CD4  FoxP3  CXCR5  CXCR3  PD-1 cells were compared before and after disease-modifying anti-rheumatic drug treatment. Cytokine levels in plasma and cytokine secretion in CD4 cells were measured and their correlations with CD4  FoxP3  CXCR5  CXCR3  PD-1 cells were further analyzed.

Results: The levels of CD4  FoxP3  CXCR5  CXCR3  PD-1 cells in the peripheral blood of patients with active RA were significantly increased compared with healthy controls. CD4  FoxP3  CXCR5  CXCR3  PD-1 cells in patients with active RA were positively correlated with serum IgG and DAS28 scores. CD4  FoxP3  CXCR5  CXCR3  PD-1 cells were significantly decreased in patients after treatment. Plasma interleukin-10 concentrations and interleukin-10-positive CD4 cell percentages were significantly positively correlated with CD4  FoxP3  CXCR5  CXCR3  PD-1 cell levels.

Conclusion: Circulating CD4  FoxP3  CXCR5  CXCR3  PD-1 cells in patients with active RA are increased and could reflect the severity of the disease, which may play a potential role in the pathogenesis of RA.
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http://dx.doi.org/10.1111/1756-185X.14170DOI Listing
August 2021

Prenatal Genetic Counseling in a Chinese Pregnant Woman With Rare Thalassemia: A Case Report.

Front Genet 2021 28;12:670168. Epub 2021 May 28.

Department of Endocrinology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Prenatal genetic counseling can be difficult, especially when it is related to fetuses with a rare thalassemia. An intronic variant located far from obvious regulatory sequences in the gene could be very difficult to evaluate as it may affect the mRNA processing or cause β-thalassemia (β-thal). In the present study, a Chinese pregnant woman with HbJ-Bangkok and a very rare change in the second intron of the gene [IVS-II-806(G>C), NM_000518.4, : c.316-45G>C] in combination with α+-thalassemia was reported, which can assist in prenatal genetic counseling. A 26-year-old pregnant woman presented at the obstetric clinic for a routine pregnancy check at 12 weeks of gestation. Red blood counts and high-performance liquid chromatography (HPLC) were consistent with clinical manifestations of anemia. Multiplex gap-polymerase chain (gap-PCR) displayed rightward deletion (-α/αα). Direct DNA sequencing of the δ-globin gene showed no mutation. Sanger sequencing of the β-globin gene showed a previously undescribed condition of double heterozygosity for HbJ-Bangkok and a very rare change in the second intron of the gene [IVS-II-806(G>C), NM_000518.4, : c.316-45G>C] that has not been previously reported in the HbVar database. Thus, a rare combination of α+-thal and a compound heterozygosity of HbJ-Bangkok and [IVS-II-806(G>C)] with α+-thal (-α/αα) was finally diagnosed. Prenatal genetic counseling was made based on the genotype and phenotype analyses. This study enlarges the mutation spectrum of β-globin gene and emphasizes DNA analysis in resolving unusual patterns in Hb analysis and the importance of sharing the observed rare undefined mutations and the possible interactions with known molecular defects, which can assist in prenatal genetic counseling.
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http://dx.doi.org/10.3389/fgene.2021.670168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194298PMC
May 2021

Structure-based molecular hybridization design of Keap1-Nrf2 inhibitors as novel protective agents of acute lung injury.

Eur J Med Chem 2021 Oct 5;222:113599. Epub 2021 Jun 5.

School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, China; School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China. Electronic address:

Blocking the Kelch-like epichlorohydrin-related protein 1 (Keap1)-nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway represents as a promising strategy to reduce oxidative stress and related-inflammation, including acute lung injury (ALI). NXPZ-2, a naphthalensulfonamide derivative, was previously reported to effectively inhibit the Keap1-Nrf2 protein-protein interaction (PPI) by our group. In the present work, a series of novel isothiocyanate-containing naphthalensulfonamides with the thioether, sulfoxide and sulfone moieties were designed by a structure-based molecular hybridization strategy using NXPZ-2 and the Nrf2 activator sulforaphane. They possessed good Keap1-Nrf2 PPI inhibitory activity and low cytotoxicity. The molecular docking study was performed to further explain the different activity of the thioether-, sulfoxide- and sulfone-containing naphthalensulfonamides. Among these new derivatives, 2-((N-(4-((N-(2-amino-2-oxoethyl)-4-((3-isothiocyanatopropyl)sulfinyl)phenyl)sulfonamido) naphthalen-1-yl)-4-methoxyphenyl)sulfonamido)acetamide (SCN-16) showed a good K value of 0.455 μM to disrupt the PPI. In an LPS-induced peritoneal macrophage cell model, this compound could cause a significant increase in the nuclear Nrf2 protein, decrease in the cytosolic Nrf2 protein, and further elevate the downstream protective enzymes HO-1 and NQO-1, which were better than the lead compound NXPZ-2 and sulforaphane. What's more, the production of ROS and NO and the expression of pro-inflammatory cytokine TNF-α were also suppressed. In the LPS-induced ALI model, SCN-16 could significantly reduce LPS-induced inflammations and alleviate lung injuries by triggering Nrf2 nuclear translocation. Collectively, our results suggested that SCN-16 could be a novel lead compound targeting Keap1-Nrf2 protective pathway for clinical treatment of ALI.
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http://dx.doi.org/10.1016/j.ejmech.2021.113599DOI Listing
October 2021

Reliability and validity of the Chinese version of the Work-Family-School Role Conflicts Scale among nurses.

Int J Nurs Sci 2021 Apr 1;8(2):221-226. Epub 2021 Mar 1.

Medicine and Health College of Lishui University, Lishui, China.

Objective: To translate and validate the Chinese version of the Work-Family-School Role Conflicts Scale (WFSRCs-S) among nurses with multiple roles.

Methods: A sample of 233 registered nurses pursuing an advanced degree was recruited from 8 university hospitals in 5 cities in China from March to July 2016. The original scale of WFSRCs-S was translated into Chinese and revised to reflect cultural meaning, using standard translation methodology, and its reliability and validity were assessed.

Results: The content validity index of the 12-item WFSRCs-S-Chinese was 0.83, and the item level of content validity index ranged from 0.79 to 1.00. The exploratory factor analysis yielded a three-factor solution (work-school-to-family role conflict, family-school-to-work role conflict, and work-family-to-school role conflict) and explained 71.9% of the total variance for WFSRCs-S-Chinese. The Cronbach's α coefficients for the total scale and the three sub-scales were 0.87, 0.79, 0.78, and 0.87. The confirmatory factor analysis revealed that the measurement model was satisfied, and the test-retest reliability of WFSRCs-S-Chinese was 0.85. The WFSRCs-S-Chinese score was positively associated with burnout ( = 0.36,  < 0.001) and negatively related to role-related social support ( = -0.18,  = 0.046), thereby establishing concurrent validity.

Conclusion: The reliability and construct validity of the WFSRCs-S-Chinese suggest that this scale could be useful to assess inter-role conflicts among nurses with multiple roles in China.
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http://dx.doi.org/10.1016/j.ijnss.2021.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105535PMC
April 2021

Bigu-Style Fasting Affects Metabolic Health by Modulating Taurine, Glucose, and Cholesterol Homeostasis in Healthy Young Adults.

J Nutr 2021 Aug;151(8):2175-2187

Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.

Background: Dynamic orchestration of metabolic pathways during continuous fasting remains unclear.

Objective: We investigated the physiological effects of Bigu-style fasting and underlying metabolic reprogramming in healthy adults.

Methods: We conducted a 5-d Bigu trial in 43 healthy subjects [age 23.2 ± 2.4 y; BMI (in kg/m2) 22.52 ± 1.79]. Physiological indicators and body composition were monitored daily during fasting day 1 (F1D) to F5D and after 10-d refeeding postfasting (R10D) and R30D. Blood samples were collected in the morning. Risk factors associated with inflammation, aging, cardiovascular diseases, malnutrition, and organ dysfunction were evaluated by biochemical measurements. Untargeted plasma metabolomics and gut microbial profiling were performed using plasma and fecal samples. Data were analyzed by repeated measures ANOVA with Greenhouse-Geisser correction. Correlation analyses for metabolite modules and taurine were analyzed by Spearman's rank and Pearson tests, respectively.

Results: Heart rate was accelerated throughout the fasting period. Risk factors associated with inflammation and cardiovascular diseases were significantly lowered during or after Bigu (P < 0.05). Body composition measurement detected an overconsumption of fat starting from F3D till 1 mo after refeeding. Metabolomics unveiled a coupling between gluconeogenesis and cholesterol biosynthesis beyond F3D. Plasma taurine significantly increased at F3D by 31%-46% followed by a reduction to basal level at F5D (P < 0.001), a pattern inversely correlated with changes in glucose and de novo synthesized cholesterol (r = -0.407 and -0.296, respectively; P < 0.001). Gut microbial profiling showed an enrichment of taurine-utilizing bacteria at F5D, which was completely recovered at R10D.

Conclusions: Our data demonstrate that 5-d Bigu is potentially beneficial to health in young adults. A starvation threshold of 3-d fasting is necessary for maintaining glucose and cholesterol homeostasis via a taurine-microbiota regulatory loop. Our findings provide novel insights into the physiological and metabolic responses of the human body to continuous Bigu-style fasting. This trial was registered at http://www.chictr.org.cn as ChiCTR1900022917.
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http://dx.doi.org/10.1093/jn/nxab123DOI Listing
August 2021

Enantiomeric profiling of a chiral benzothiazole necroptosis inhibitor.

Bioorg Med Chem Lett 2021 07 6;43:128084. Epub 2021 May 6.

School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004, China; School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China. Electronic address:

Necroptosis is a form of programmed cell death that contributes to the pathophysiology of multiple diseases. Development of small-molecule anti-necroptosis agents has great promising clinical therapeutic relevance. The benzothiazole compounds were discovered by our group from an in-house fluorine-containing compound library as potent necroptosis inhibitors. Herein, a chiral dimethylcyclopropyl benzothiazole necroptosis inhibitor was developed and the enantiomeric profiling resulted that the (S) form was generally more potent than the (R) counterpart in 2 ~ 4-fold toward cell necroptosis, receptor-interacting protein (RIP) kinases 1 and 3. The chiral compounds could significantly inhibit the expression of the phosphorylation of RIPK1, RIPK3 and MLKL in necroptotic cells. The molecular modelling studies predicted the binding modes of the enantiomers with RIP and explained their activity differences, guiding further rational design of the chiral necroptosis inhibitors.
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http://dx.doi.org/10.1016/j.bmcl.2021.128084DOI Listing
July 2021

A Glycolysis-Related Five-Gene Signature Predicts Biochemical Recurrence-Free Survival in Patients With Prostate Adenocarcinoma.

Front Oncol 2021 19;11:625452. Epub 2021 Apr 19.

Department of Endocrinology and Diabetes Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Prostate cancer (PCa) is one of the most frequently diagnosed cancers in males worldwide. Approximately 25% of all patients experience biochemical recurrence (BCR) after radical prostatectomy (RP) and BCR indicates increased risk for metastasis and castration resistance. PCa patients with highly glycolytic tumors have a worse prognosis. Thus, this study aimed to explore glycolysis-based predictive biomarkers for BCR. Expression data and clinical information of PCa samples were retrieved from three publicly available datasets. One from The Cancer Genome Atlas (TCGA) dataset was used as the training cohort, and two from the Gene Expression Omnibus (GEO) dataset (GSE54460 and GSE70769) were used as validation cohorts. Using the training cohort, univariate Cox regression survival analysis, robust likelihood-based survival model, and stepwise multiply Cox analysis were sequentially applied to explore predictive glycolysis-related candidates. A five-gene risk score was then constructed based on the Cox coefficient as the following: (-0.8367*GYS2) + (0.3448*STMN1) + (0.3595*PPFIA4) + (-0.1940*KDELR3) + (0.4779*ABCB6). Receiver operating characteristic curve (ROC) analysis was used to identify the optimal cut-off point, and patients were divided into low risk and high risk groups. Kaplan-Meier analysis revealed that high risk group had significantly shorter BCR free survival time as compared with that in low risk group in training and validation cohorts. In conclusion, our data support the glycolysis-based five-gene signature as a novel and robust signature for predicting BCR of PCa patients.
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http://dx.doi.org/10.3389/fonc.2021.625452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092437PMC
April 2021

Structure-based bioisosterism design of thio-benzoxazepinones as novel necroptosis inhibitors.

Eur J Med Chem 2021 Aug 27;220:113484. Epub 2021 Apr 27.

School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai, 200433, China; School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, China. Electronic address:

Necroptosis is reported to play a critical role in contributing to a variety of human pathologies. The benzoxazepinone GSK'772 is a potent necroptosis inhibitor optimized using a hit from a DNA-encoded library, which is currently in phase II clinical trials for psoriasis, rheumatoid arthritis, and ulcerative colitis. In the present study, the bioisosterism strategy was applied to replace the amide and benzene ring of GSK'772 based on the co-crystal structure of GSK'772 with its binding target RIPK1. As a result, the novel thio-benzoxazepinones exhibited higher anti-necroptosis activity in a human HT-29 cell necroptosis model. The effect on anti-necroptosis activity by the chirality was significantly reduced in the thio-benzoxazepinones, which was explained by the ligand conformation calculation. Among these analogues, compound 11 (S) and 12 (R) specifically inhibited necroptosis rather than apoptosis with EC values of 2.8 and 22.6 nM. They blocked necrosome formation by inhibiting the phosphorylation of RIPK1, RIPK3 and MLKL in necroptotic cells. Collectively, the highly potent thio-benzoxazepinones represent promising lead structures for further development of necroptosis-related diseases.
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http://dx.doi.org/10.1016/j.ejmech.2021.113484DOI Listing
August 2021

Ketogenic diet and growth in Chinese infants with refractory epilepsy.

Asia Pac J Clin Nutr 2021 ;30(1):113-121

Department of Nutrition, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders. Email:

Background And Objectives: This study evaluated the impact of 12 months of ketogenic dietary treatment (KDT) on growth in Chinese infants with refractory epilepsy.

Methods And Study Design: The KDT group included patients who were divided into groups A (age 6-12 months), B (12-24 months) and C (24-36 months). The normal group included infants aged approximately 6-12 months, 12-24 months and 24-36 months who were classified into groups A1, B1 and C1, respectively. Data on height, weight, aspartate transaminase (AST), alanine transaminase (ALT), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), zinc, iron, calcium, magnesium, and haemoglobin (Hb) were extracted from the medical records. Then, we compared the impacts of 12 months of KDT on growth.

Results: Forty-one patients were included in the KDT group, and 90 infants were included in the normal group. The overall prevalence of underweight (WAZ <-2 SD), stunting (HAZ <-2 SD), wasting (BAZ <-2 SD), and overweight/obesity (BAZ ≥2 SD) were relatively lower in the A and B groups. The prevalence of anaemia in group A was significantly higher than that in group A1. No significant differences were observed in the KDT groups with regard to HDL, LDL, AST, ALT, iron, calcium, magnesium, or zinc. A greater than 50% reduction in weekly seizure frequency was evident in 100% of group A, 78.6% of group B and 77.8% of group C.

Conclusions: The results revealed that patients less than 2 years old who received KDT maintained appropriate growth at the 12-month follow-up.
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http://dx.doi.org/10.6133/apjcn.202103_30(1).0014DOI Listing
January 2021

Anti-freezing, moisturizing, resilient and conductive organohydrogel for sensitive pressure sensors.

J Colloid Interface Sci 2021 Jul 19;594:584-592. Epub 2021 Mar 19.

MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage, School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin 150001, China. Electronic address:

Conductive hydrogels have attracted significant attention in the area of wearable pressure sensors due to their mechanical flexibility, conductivity and self-healing capability. At subzero temperatures, water-based conductive hydrogels unavoidably lose their elasticity and conductivity which limits their practical usages at low temperatures. However, traditional conductive hydrogels are short of moisturizing and anti-freezing ability due to the limitation of pure water solvent, which greatly restricts their application in extreme environments. In this study, an anti-freezing and moisturizing conductive double network organohydrogel was prepared by incorporating thioctic acid (TA) with polyvinyl alcohol-borate (PVA-PB) in carbon nanotubes (CNTs) that were dispersed in water (HO) and ethylene glycol (EG). The as-prepared PVA-B-TA-CNTs organohydrogel presented outstanding anti-freezing performance (-60 C), long-term moisturizing property (30 days), excellent stability (400 cycles) and fascinating conductive sensitivity (S = 0.625 kPa). The occurrence of dynamic covalent disulfide bonds and noncovalent hydrogen bonds endow the conductive organohydrogels with brilliant remoldability and self-healing ability, which are significant for practical applications. These remarkable advantages make PVA-B-TA-CNTs organohydrogel to have enormous potential in the application of wearable and flexible pressure sensors, human-healthy monitor, and intelligence devices.
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http://dx.doi.org/10.1016/j.jcis.2021.03.079DOI Listing
July 2021

Altered follicular regulatory T (Tfr)- and helper T (Tfh)-cell subsets are associated with autoantibody levels in microscopic polyangiitis patients.

Eur J Immunol 2021 Jul 23;51(7):1809-1823. Epub 2021 Apr 23.

Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is an autoimmune disease characterized by B cells-derived ANCAs, and ANCA was proved to be a key factor in its pathogenesis. Follicular regulatory T (Tfr) and follicular helper T (Tfh) cells were T-cell subsets that play important roles in B-cell maturation and antibody production. However, their significances in microscopic polyangiitis (MPA) patients, one type of AAV, has not been thoroughly studied. In this study, comprehensive pattern analyses of circulating Tfr and Tfh were performed in MPA patients and healthy controls (HCs), and we found Tfr levels and Tfr/Tfh ratios were significantly decreased in MPA patients. Compared with HCs, Helios+, CD45RA-FoxP3hi, and Ki-67+ Tfr were lower in MPA patients, while CD226+ Tfr cells were higher. These phenotypes suggest that function and proliferation ability of Tfr cells were relatively impaired. Tfh subsets, including ICOS+PD-1+ and Ki-67+ Tfh, were significantly increased, suggesting that the function of Tfh was enhanced in MPA although the total Tfh levels did not change significantly. Circulating memory B cells and plasmablasts were significantly elevated and negatively correlated with Tfr levels and Tfr/Tfh ratios in MPA patients. In addition, Tfr levels and Tfr/Tfh ratios were negatively while Tfh was positively correlated with serum myeloperoxidase (MPO)-ANCA levels. Furthermore, Tfr and Tfr/Tfh ratio were also reversely associated with SCr, BUN, IL-4, and IL-21 levels. Our results suggest that the imbalance of Tfr and Tfh functional subsets is related to increased level of autoantibodies in MPA patients, and we propose a new mechanism for the pathogenesis of MPA.
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http://dx.doi.org/10.1002/eji.202049093DOI Listing
July 2021

Increased circulating PD-1CXCR5- peripheral helper T cells are associated with disease severity of active ulcerative colitis patients.

Immunol Lett 2021 May 3;233:2-10. Epub 2021 Mar 3.

Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China. Electronic address:

Purpose: A recently identified population of T cells, phenotypically CD4PD-1CXCR5, has been firstly termed as peripheral helper T cells (Tph) and found to be pathogenic in autoimmune diseases. However, the potential role of Tph in ulcerative colitis (UC) remains unclear. We aim to investigate the changes of circulating Tph in UC patients and their potential significance in the pathogenesis of UC.

Methods: Totally 68 UC patients and 34 age- and sex-matched healthy controls were enrolled. Circulating Tph and B cell subsets were analyzed by flow cytometry. Expressions of inducible T-cell co-stimulator (ICOS) on Tph cells were analyzed. Serum IL-4, IL-10, IL-12 and IL-21 were detected using ELISA. Correlation analyses were conducted between Tph cells and disease severity, functional B cell subsets and serum cytokines.

Results: Both the frequency and absolute number of Tph were significantly increased in active UC patients and ICOS levels in Tph cells were also elevated, compared with remission UC patients and healthy controls. Tph and ICOS expression were significantly positively correlated with Mayo score and serum CRP in active UC patients, and were significantly decreased when achieving remission after treatment. Tph levels were correlated with new memory B cells, plasmablasts, serum IL-4 and IL-21. Meanwhile, serum IL-10 showed negative correlation while IL-12 exhibited positive correlation with circulating Tph cells in UC patients.

Conclusions: Circulating Tph cells are elevated in active UC patients and are associated with the disease activity, which may contribute to the pathogenesis of UC.
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http://dx.doi.org/10.1016/j.imlet.2021.03.001DOI Listing
May 2021

CircRNA_103765 acts as a proinflammatory factor via sponging miR-30 family in Crohn's disease.

Sci Rep 2021 01 12;11(1):565. Epub 2021 Jan 12.

Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, 215008, Jiangsu, China.

Increasing evidence suggests that circular RNAs (circRNAs) play critical roles in various pathophysiological activities. However, the role of circRNAs in inflammatory bowel disease (IBD) remains unclear. Here we report the potential roles of hsa_circRNA_103765 in regulating cell apoptosis induced by TNF-α in Crohn's disease (CD). We identify that CircRNA_103765 expression was significantly upregulated in peripheral blood mononuclear cells (PBMCs) of patients with active IBD. A positive correlation with TNF-α significantly enhanced circRNA_103765 expression in CD, which was significantly reversed by anti-TNF-α mAb (infliximab) treatment. In vitro experiments showed that TNF-α could induce the expression of circRNA_103765, which was cell apoptosis dependent, while silencing of circRNA_103765 could protect human intestinal epithelial cells (IECs) from TNF-α-induced apoptosis. In addition, circRNA_103765 acted as a molecular sponge to adsorb the miR-30 family and impair the negative regulation of Delta-like ligand 4 (DLL4). Collectively, CircRNA_103765 is a novel important regulator of the pathogenesis of IBD via sponging miR-30 family-mediated DLL4 expression changes. Blockade of circRNA_103765 could serve as a novel approach for the treatment of IBD patients.
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http://dx.doi.org/10.1038/s41598-020-80663-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804428PMC
January 2021

A novel negative pressure drainage treatment of auricular pseudocyst.

Am J Otolaryngol 2021 Mar-Apr;42(2):102863. Epub 2020 Dec 29.

Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, Medical College of Zhejiang University, Hangzhou, China. Electronic address:

Objective: Pseudocyst of the auricle is a benign cystic lesions of the ear. A variety of methods have been proposed priorly with different treatment effects. Although aggressive treatments may have good results, we aimed to introduce a less invasive method that also yield optimal cosmetic outcome.

Patients And Methods: From August 2019 to April 2020, a total of 32 patients with pseudocyst of the auricle were treated with a novel negative pressure drainage method.

Results: The treatment has performed successfully in all patients. Only 2 patients experienced negative pressure drainage device detachment, and recovered smoothly after reinstallment. Patients were followed up for an average period of 3 months. The appearance of the auricle was recovered excellent in all patients. There were no postoperative complications or episodes of recurrence during the follow-up period.

Conclusion: Considering the excellent cosmetic outcome and free of recurrence, we would recommend our negative pressure drainage method as a first-line treatment for all patients with auricular pseudocyst.
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http://dx.doi.org/10.1016/j.amjoto.2020.102863DOI Listing
September 2021

Positive Rate of Serology and RT-PCR for COVID-19 among Community Residents and Healthcare Workers in Wuhan, China.

Jpn J Infect Dis 2021 Jul 25;74(4):333-336. Epub 2020 Dec 25.

Department of Ophthalmology, Renmin Hospital of Wuhan University, China.

This study aimed to evaluate the infection rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among different populations in Wuhan, China. This cross-sectional survey-based study examined the results of SARS-CoV-2-specific serological tests and RT-PCR tests for 4,454 community residents and 4,614 healthcare workers performed from May 15 to May 29, 2020. The healthcare workers were classified as administrative and logistical staff (n = 1,378), non-first-line healthcare workers (n = 2,630), or first-line healthcare workers (n = 606) according to their frequency of contact with coronavirus disease (COVID-19) patients. The positive rates of SARS-CoV-2-specific IgG, IgM, and RNA were 2.9%, 0.4%, and 0.1% for the community residents and 3.3%, 0.6%, and 0.2% for the healthcare workers, respectively. There were no statistically significant differences between the rates of the two groups. Spearman's correlation analysis showed that the frequency of contact with COVID-19 patients negatively correlated with the positive rates of RT-PCR (r = -0.036, P = 0.016), but did not significantly correlate with the positive rates of IgM (r = -0.006, P = 0.698) or IgG (r = 0.017, P = 0.239). There was no statistically significant difference between the SARS-CoV-2-specific IgG, IgM, or RNA positive rates of the community residents and those of the healthcare workers. The positive rate of SARS-CoV-2 RNA was lower for the first-line healthcare workers than for the non-first-line healthcare workers and the administrative and logistical staff.
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http://dx.doi.org/10.7883/yoken.JJID.2020.691DOI Listing
July 2021

Increased Circulating Th1 and Tfh1 Cell Numbers Are Associated with Disease Activity in Glucocorticoid-Treated Patients with IgG4-Related Disease.

J Immunol Res 2020 27;2020:3757015. Epub 2020 Nov 27.

Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.

Background: This study is aimed at exploring the changes and significance of circulating Th and Tfh cell subsets in glucocorticoid-treated IgG4-RD patients.

Methods: 39 glucocorticoid-treated IgG4-RD patients and 22 healthy controls (HC) were enrolled. Peripheral blood mononuclear cells were separated, and circulating Th and Tfh cell subsets were examined by flow cytometry according to the surface and intranuclear markers. Disease activity was accessed by the IgG4-RD responder index (RI) score. Correlation analyses were conducted between Th/Tfh subset numbers and clinical indicators. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of Th and Tfh subsets to distinguish active IgG4-RD patients from remission IgG4-RD patients.

Results: Circulating Th1, Th17, Tfh1, and Tfh17 cells were significantly increased in active IgG4-RD patients compared with HC. Th1 and Tfh1 numbers were positively correlated with serum IgG4 levels in patients with IgG4-RD. Meanwhile, the absolute numbers of circulating Th1 and Tfh1 cells were positively correlated with IgG4-RD RI scores. The areas under the curve (AUC) were 0.8276 for Th1 and 0.7310 for Tfh1, 0.5862 for Tfh2, and 0.6810 for Tfh17.

Conclusion: Increased circulating Th1 and Tfh1 subsets are related to elevated serum IgG4 levels in active IgG4-RD patients during glucocorticoid treatment, which may play an important role in the course of IgG4-RD disease, and could be potential biomarkers for monitoring disease activity of IgG4-RD.
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http://dx.doi.org/10.1155/2020/3757015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721509PMC
August 2021

Ubiquitin-specific protease 14 promotes radio-resistance and suppresses autophagy in oral squamous cell carcinoma.

Exp Cell Res 2021 01 16;398(2):112385. Epub 2020 Nov 16.

Clinical Laboratory, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450052, China.

Oral squamous cell carcinoma (OSCC) is a common malignant tumor in the world. Radiotherapy is one of the standard therapies for patients with OSCC, but its clinical efficiency is limited due to radioresistance. In this study, we identified a mechanism of such resistance regulated by Ubiquitin-specific protease 14 (USP14). USP14 expression was significantly increased in clinical OSCC tissue samples and cell lines, and OSCC patients with high USP14 expression predicted poor overall survival rate. Additionally, a negative correlation between USP14 and LC3B was observed in patients with OSCC. We then found that irradiation (IR)-reduced cell survival of OSCC cells lines was further decreased when USP14 was knocked down. However, USP14 over-expression significantly promoted the cell viability of OSCC cells after IR treatment. Colony formation analysis confirmed thatafter IR treatment,USP14 knockdown markedly decreased the proliferation of OSCC cells, but over-expressing USP14 significantly up-regulated the proliferative activity of OSCC cells. Furthermore, DNA damage caused by IR was enhanced by USP14 knockdown, while been suppressed in OSCC cells with USP14 over-expression. Additionally, IR-inducedapoptosis was further promoted by USP14 knockdown in OSCC cells, which was, however, significantly abolished by USP14 over-expression.Moreover, our in vivo studies showed that IR-reduced tumor growth and tumor weight were further enhanced by USP14 knockdown in OSCC tumor-bearing nude mice. Finally, we found that USP14 knockdown could promote IR-induced autophagy by increasing LC3BII and γH2AX expression levels in IR-treated OSCC cells. However, this event was markedly abolished by ATG5 knockdown, subsequently restoring the cell proliferation in IR-incubated OSCC cells.Finally, we found that USP14-mediated apoptosis was autophagy-dependent in IR-treated OSCC cells. Taken together, these findings suggested that suppressing USP14 could alleviateradioresistancein OSCC both in vitro and in vivo by inducing apoptosis and autophagy, and thus could be served as a promising therapeutic strategy for OSCC treatment.
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http://dx.doi.org/10.1016/j.yexcr.2020.112385DOI Listing
January 2021

C-C chemokine receptor 5 signaling contributes to cardiac remodeling and dysfunction under pressure overload.

Mol Med Rep 2021 01 17;23(1). Epub 2020 Nov 17.

Translational Medicine Center, Baotou Central Hospital, Donghe, Baotou 014040, P.R. China.

Aortic stenosis (AS) leads to chronic pressure overload, cardiac remodeling and eventually heart failure. Chemokines and their receptors have been implicated in pressure overload‑induced cardiac remodeling and dysfunction. In the present study, the role of C‑C chemokine receptor 5 (CCR5) in pressure overload‑induced cardiac remodeling and dysfunction was investigated in mice subjected to transverse aortic constriction (TAC). Cardiac levels of CCR5 and C‑C motif chemokine ligands (CCLs)3, 4 and 5 were determined by western blotting and reverse transcription‑quantitative PCR, respectively. Cardiac functional parameters were evaluated by echocardiographic and hemodynamic measurements. Myocardial fibrosis was assessed by Masson's trichrome staining and α‑smooth muscle actin immunostaining. Myocardial hypertrophy and inflammatory cell infiltration were evaluated by hematoxylin and eosin staining. Angiotensin II (Ang II)‑induced hypertrophy of H9c2 cardiomyocytes was assessed by F‑actin immunostaining. ERK1/2 and P38 phosphorylation was examined by western blotting. TAC mice exhibited higher myocardial CCL3, CCL4, CCL5 and CCR5 levels compared with sham mice. Compared with sham mice, TAC mice also exhibited impaired cardiac function along with myocardial hypertrophy, fibrosis and inflammatory cell infiltration. TAC‑induced cardiac remodeling and dysfunction were effectively ameliorated by administration of anti‑CCR5 but not by IgG control antibody. Mechanistically, increased ERK1/2 and P38 phosphorylation was detected in TAC hearts and Ang II‑stimulated H9c2 cardiomyocytes. Treatment with anti‑CCR5 antibody decreased ERK1/2 and P38 phosphorylation and attenuated Ang II‑induced H9c2 cell hypertrophy. CCR5 inhibition protected against pressure overload‑induced cardiac abnormality. The findings of the present study indicate that ERK1/2 and P38 signaling pathways may be involved in the cardioprotective effects of CCR5 inhibition.
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http://dx.doi.org/10.3892/mmr.2020.11687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716393PMC
January 2021

Construction of Microunits by Adipose-Derived Mesenchymal Stem Cells Laden with Porous Microcryogels for Repairing an Acute Achilles Tendon Rupture in a Rat Model.

Int J Nanomedicine 2020 29;15:7155-7171. Epub 2020 Sep 29.

Department of Orthopedic Surgery, Key Laboratory of Musculoskeletal Trauma &war Injuries PLA, Beijing Key Laboratory of Regenerative Medicine in Orthopedics, Chinese PLA General Hospital, Beijing 100853, People's Republic of China.

Objective: Tissue engineering approaches seem to be an attractive therapy for tendon rupture. Novel injectable porous gelatin microcryogels (GMs) can promote cell attachment and proliferation, thus facilitating the repair potential for target tissue regeneration. The research objectives of this study were to assess the efficacy of tissue-like microunits constructed by multiple GMs laden with adipose-derived mesenchymal stem cells (ASCs) in accelerated tendon regeneration in a rat model.

Methods: Through a series of experiments, such as isolation and identification of ASCs, scanning electron microscopy, mercury intrusion porosimetry (MIP), laser scanning confocal microscopy and the CCK-8 test, the biocompatibility of GMs was evaluated. In an in vivo study, 64 rat right transected Achilles tendons were randomly divided into four groups: the ASCs+GMs group (microunits aggregated by multiple ASC-laden GMs injected into the gap), the ASCs group ( injected into the gap), the GMs group (GMs injected into the gap) and the blank defect group (non-treated). At 2 and 4 weeks postoperatively, the healing tissue was harvested to evaluate the gross observation and scoring, biomechanical testing, histological staining and quantitative scoring. Gait analysis was performed over time. The 64 rats were randomly assigned into 4 groups: (1) micro-unit group (ASCs+GMs) containing ASC (10)-loaded 120 GMs in 60 μL DMEM; (2) cell control group (ASCs) containing 10 ASCs in 60 μL DMEM; (3) GM control group (GMs) containing 120 blank GMs in 60 μL DMEM; (4) blank defect group (Defect) containing 60 μL DMEM, which were injected into the defect sites. All animals were sacrificed at 2 and 4 weeks postsurgery (Table 1).

Results: In an in vitro study, GMs (from 126 μm to 348 μm) showed good porosities and a three-dimensional void structure with a good interpore connectivity of the micropores and exhibited excellent biocompatibility with ASCs. As the culture time elapsed, the extracellular matrix (ECM) secreted by ASCs encased the GMs, bound multiple microspheres together, and then formed active tendon tissue-engineering microunits. In animal experiments, the ASCs+GMs group and the ASCs group showed stimulatory effects on Achilles tendon healing. Moreover, the ASCs+GMs group was the best at improving the macroscopic appearance, histological morphology, Achilles functional index (AFI), and biomechanical properties of repair tissue without causing adverse immune reactions.

Conclusion: Porous GMs were conducive to promoting cell proliferation and facilitating ECM secretion. The ASCs-GMs matrices showed an obvious therapeutic efficiency for Achilles tendon rupture in rats.
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http://dx.doi.org/10.2147/IJN.S238399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535144PMC
November 2020

Ion-mediated self-assembly of Cys-capped quantum dots for fluorescence detection of As(iii) in water.

Anal Methods 2020 09 21;12(34):4229-4234. Epub 2020 Aug 21.

Hunan Province Microbiology Institute, Changsha, Hunan 410009, P. R. China.

A sensitive As(iii) ion detection method has been developed based on ion-mediated self-assembly of cysteine (Cys)-capped quantum dots (QDs), and fluorescence self-quenching. A variety of Cys-capped core/shell CdTe/CdS QDs were prepared via hydrothermal methods. Based on the coordination binding between the As(iii) ion and cystine groups anchored on the QDs, addition of As(iii) ions led to self-assembly of the Cys-capped QDs, which was accompanied by fluorescence self-quenching. The fluorescence response was attributed to the exciton energy transfer of the QD aggregates. The ion-mediated fluorescence quenching was further exploited for quantitative determination of As(iii) ions in water. A limit of detection (LOD) of 10 ng L (3σ method) and a linear range from 14 to 70 ng L were obtained for the sensing of As(iii) ions. The system was evaluated using a series of interference targets, and demonstrated high selectivity after addition of mask agents. Finally, the proposed method was successfully employed for the detection of As(iii) in a real water sample. The method was sensitive and specific, and shows great promise in quantitative determination of heavy metal ions in lakes and rivers.
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http://dx.doi.org/10.1039/d0ay01144dDOI Listing
September 2020

An iPSC line (TYWHSTi002-A) derived from a patient with Pendred syndrome caused by compound heterozygous mutations in the SLC26A4 gene.

Stem Cell Res 2020 Jul 20;47:101919. Epub 2020 Jul 20.

Medical College of Wuhan University of Science and Technology, Wuhan, China.

Pendred syndrome (PDS) is hereditary and is characterized by thyroid enlargement, cochlea abnormalities, and hearing impairment. In this study, we established an induced pluripotent stem cell line from a PDS patient with familial thyroid disorder, caused by compound heterozygous mutations in SLC26A4 (NM_000441.1; c.919-2A>G and c.1614 + 1G>A). Isolated peripheral blood mononuclear cells of the patient were reprogrammed using the transgene free Sendai viral vectors, encoding SOX2, OCT4, KLF4, and cMYC. The resulting iPSC line was verified based on morphology, pluripotency markers, and differentiation potential into all three germ layers, and demonstrated typical features in accordance with those of embryo stem cells.
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http://dx.doi.org/10.1016/j.scr.2020.101919DOI Listing
July 2020

Prior bariatric surgery and perioperative cardiovascular outcomes following noncardiac surgery in patients with type 2 diabetes mellitus: hint from National Inpatient Sample Database.

Cardiovasc Diabetol 2020 07 6;19(1):103. Epub 2020 Jul 6.

Department of Endocrinology, The First Affiliated Hospital, Sun Yat-Sen University, No. 58, Zhong Shan Er Lu, Guangzhou, 510080, China.

Background: Both diabetes and obesity are risk factors for perioperative major adverse events. This study aims to evaluate the association between prior bariatric surgery (prior-BS) and perioperative cardiovascular outcomes following noncardiac surgery in patients with type 2 diabetes mellitus (T2DM).

Methods: We used the National Inpatient Sample Database to identify T2DM patients undergoing major noncardiac surgery from 2006 to 2014. The primary outcome was major perioperative adverse cardiovascular and cerebrovascular events (MACCEs), which include death, acute myocardial infarction and acute ischaemic stroke. In-hospital outcomes between patients with prior BS and morbid obesity were compared using unadjusted logistic, multivariable logistic and propensity score matching analyses.

Results: A weighted of 1,526,820 patients diagnosed with T2DM who underwent noncardiac surgery were included. The rates of both prior BS and morbid obesity significantly increased during the study period (P < 0.0001). Patients with prior BS were younger, were more likely to be female, and had lower rates of cardiovascular risk factors but had higher rates of smoking, alcohol abuse, anaemia, prior venous thromboembolism and prior percutaneous coronary intervention. The incidence of MACCEs was 1.01% and 3.25% in patients with prior BS and morbid obesity, respectively. After multivariable adjustment, we found that prior BS was associated with a reduced risk of MACCEs (odds ratio [OR] = 0.71; 95% confidence interval [CI] 0.62-0.81), death (OR = 0.64, 95% CI 0.52-0.78), acute kidney injury (OR = 0.66, 95% CI 0.62-0.70) and acute respiratory failure (OR: 0.46; 95% CI 0.42-0.50).

Conclusions: Prior bariatric surgery in T2DM patients undergoing noncardiac surgery is associated with a lower risk of MACCEs. Prospective studies are needed to verify the benefits of bariatric surgery in patients undergoing noncardiac surgery.
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http://dx.doi.org/10.1186/s12933-020-01084-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339406PMC
July 2020

A novel thrombin-based triagonist with diabetes-protective and weight-lowering potential.

Life Sci 2020 Sep 26;256:117853. Epub 2020 May 26.

The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, PR China.

Aims: To investigate the diabetes-protective effect and weight-lowering potential of a novel long-acting triagonist at three metabolically related hormone receptors including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon receptors.

Main Methods: Triagonist were designed in an iterative manner from native GLP-1, GIP and Glucogan. Main peptide chain (termed TG peptides) and subsequently modified LTG peptides were synthesized via solid phase synthesis. In vitro receptor activity assay was performed to screen the TG peptide with most balanced potency on all three receptors. The in vitro biological activities of modified TG peptides were further investigated by albumin-binding measurement and proteolytic cleavage test. Subsequently, oral glucose tolerance test (OGTT), pharmacokinetic test and chronic study were subjected to the acute and long-term efficacy evaluation of selected fusion peptide, LTG-6.

Key Findings: TG-8 exhibited equally aligned constituent efficacy and supraphysiological potency on corresponding receptor without cross-reactivity. Modified TG-8, termed LTG-6, exerted the great binding affinity for human serum albumin and the enhanced rational controlled-release of TG-8 in vitro. Further OGTT in different gene knockout mice and diabetic mice demonstrated the promising hypoglycemic and insulinotropic abilities of LTG-6. After long-term treatment for 8 weeks, LTG-6 was proved superior to co-agonists to decrease the body weight and %HbA1c, improve reverse dyslipidemia and glycemic control in the DIO models.

Significance: LTG-6, as a newly designed long-acting triagonist, holds potential to correct the obesity related metabolic disorders.
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http://dx.doi.org/10.1016/j.lfs.2020.117853DOI Listing
September 2020
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