Publications by authors named "Lihua Sun"

208 Publications

Impacts of Diagnosis-Related Groups Payment on the Healthcare Providers' Behavior in China: A Cross-Sectional Study Among Physicians.

Risk Manag Healthc Policy 2021 1;14:2263-2276. Epub 2021 Jun 1.

College of Business Administration, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.

Purpose: Currently, China is piloting diagnosis-related groups (DRG) payment system in 30 cities. The main aim of this study was to explore the respondents' impressions regarding the hospitals' policies and physicians' behavior change brought by the DRG payment system, and investigate whether and how the hospitals' policies affect the physicians' behavior.

Methods: We distributed questionnaires designed for this study to 200 physicians. Data analysis consisted of descriptive statistics, -test, and network analysis.

Results: Respondents stated that the hospitals had adopted several policies in response to DRG payment and DRG payment could reduce overtreatment and improve efficiency. However, it also led to several negative effects including an increased explanation to the patients, hindering new technologies, case splitting, and cherry picking. In addition, there was no evidence that harmful effects such as refusing patients and premature discharge existed. Overall, the benefits outweighed the drawbacks of DRG. Moreover, the hospitals' policies could effectively change physician behaviors. Our results indicated that promoting the implementation of clinical pathways had the most positive impact, while limiting costs and length of stay is not recommended.

Conclusion: In general, Chinese physicians who participated in the questionnaire possessed relatively positive attitudes towards the DRG payment system. Nevertheless, some of the negative impacts cannot be ignored. Meanwhile, the hospitals' policies should be implemented with adequate consideration of the impact on physicians' behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/RMHP.S308183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180304PMC
June 2021

A Novel Role of AR in the Maintenance of Intestinal Barrier Function of Enteric Glia from Hypoxia-Induced Injury by Combining with mGluR5.

Front Pharmacol 2021 10;12:633403. Epub 2021 May 10.

Department of General Surgery, Xinqiao Hospital, Army Medical University, Chongqing, China.

During acute intestinal ischemia reperfusion (IR) injury, the intestinal epithelial barrier (IEB) function is often disrupted. Enteric glial cells (EGCs) play an important role in maintaining the integrity of IEB functions. However, how EGCs regulate IEB function under IR stimulation is unknown. The present study reveals that the adenosine A receptor (AR) is important for mediating the barrier-modulating roles of EGCs. AR knockout (KO) experiments revealed more serious intestinal injury in AR KO mice than in WT mice after IR stimulation. Moreover, AR expression was significantly increased in WT mice when challenged by IR. To further investigate the role of AR in IEB, we established an EGC-Caco-2 co-culture system. Hypoxia stimulation was used to mimic the process of IR. Treating EGCs with the CGS21680 AR agonist attenuated hypoxia-induced intestinal epithelium damage through up-regulating ZO-1 and occludin expression in cocultured Caco-2 monolayers. Furthermore, we showed that AR and metabotropic glutamate receptor 5 (mGluR5) combine to activate the PKCα-dependent pathway in conditions of hypoxia. This study shows, for the first time, that hypoxia induces AR-mGluR5 interaction in EGCs to protect IEB function via the PKCα pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.633403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173626PMC
May 2021

Quantum walks on a programmable two-dimensional 62-qubit superconducting processor.

Science 2021 05 6;372(6545):948-952. Epub 2021 May 6.

National Institute of Informatics, 2-1-2 Hitotsubashi, Chiyoda-ku, Tokyo 101-8430, Japan.

Quantum walks are the quantum mechanical analog of classical random walks and an extremely powerful tool in quantum simulations, quantum search algorithms, and even for universal quantum computing. In our work, we have designed and fabricated an 8-by-8 two-dimensional square superconducting qubit array composed of 62 functional qubits. We used this device to demonstrate high-fidelity single- and two-particle quantum walks. Furthermore, with the high programmability of the quantum processor, we implemented a Mach-Zehnder interferometer where the quantum walker coherently traverses in two paths before interfering and exiting. By tuning the disorders on the evolution paths, we observed interference fringes with single and double walkers. Our work is a milestone in the field, bringing future larger-scale quantum applications closer to realization for noisy intermediate-scale quantum processors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.abg7812DOI Listing
May 2021

LncRNA MIAT impairs cardiac contractile function by acting on mitochondrial translocator protein TSPO in a mouse model of myocardial infarction.

Signal Transduct Target Ther 2021 May 3;6(1):172. Epub 2021 May 3.

Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China and Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, P. R. China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41392-021-00538-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093248PMC
May 2021

HDAC2 enhances esophageal squamous cell carcinoma development through down-regulating microRNA-503-5p and promoting CXCL10.

Clin Epigenetics 2021 Apr 29;13(1):96. Epub 2021 Apr 29.

Department of Thoracic Surgery, The Second Hospital of Jilin University, NO. 218 Ziqiang Street, Changchun, 130041, Jilin, China.

Objective: Although esophageal squamous cell carcinoma (ESCC)-oriented mechanism has been widely explored, the integrated action of histone deacetylase 2 (HDAC2), microRNA (miR)-503-5p and C-X-C motif chemokine 10 (CXCL10) in ESCC has not been thoroughly explored. Thus, we performed the research to study the role of HDAC2/miR-503-5p/CXCL10 axis in ESCC.

Methods: ESCC tissues and mucosal tissues (5 cm from cancer tissues) were collected, in which HDAC2, miR-503-5p and CXCL10 expression levels were tested. The mechanism of HDAC2, miR-503-5p and CXCL10 was interpreted. The viability, colony formation ability, apoptosis, invasion and migration abilities of ESCC cells were tested after HDAC2, miR-503-5p or CXCL10 expression was altered. Tumorigenesis in mice was observed to further verify the in vitro effects of HDAC2 and miR-503-5p.

Results: HDAC2 and CXCL10 were up-regulated while miR-503-5p was down-regulated in ESCC. HDAC2 bound to miR-503-5p and miR-503-5p targeted CXCL10. Silencing HDAC2 or restoring miR-503-5p depressed viability, colony-forming, invasion and migration abilities and enhanced apoptosis of ESCC cells in vitro, as well as suppressed ESCC tumorigenesis in vivo. Inhibition of miR-503-5p or elevation of CXCL10 negated HDAC2 knockout-induced effects on ESCC cells.

Conclusion: This work elucidates that HDAC2 knockdown retards the process of ESCC by elevating miR-503-5p and inhibiting CXCL10 expression, which may provide a guidance for ESCC management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13148-021-01068-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082674PMC
April 2021

Strengthened luteal phase support for patients with low serum progesterone on the day of frozen embryo transfer in artificial endometrial preparation cycles: a large-sample retrospective trial.

Reprod Biol Endocrinol 2021 Apr 23;19(1):60. Epub 2021 Apr 23.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.

Background: Low serum progesterone on the day of frozen embryo transfer (FET) is associated with diminished pregnancy rates in artificial endometrium preparation cycles, but there is no consensus on whether strengthened luteal phase support (LPS) benefits patients with low progesterone on the FET day in artificial cycles. This single-centre, large-sample retrospective trial was designed to investigate the contribution of strengthened LPS to pregnancy outcomes for groups with low progesterone levels on the FET day in artificial endometrium preparation cycles.

Methods: Women who had undergone the first artificial endometrium preparation cycle after a freeze-all protocol in our clinic from 2016 to 2018 were classified into two groups depending on their serum progesterone levels on the FET day. Routine LPS was administered to group B (P ≥ 10.0 ng/ml on the FET day, n = 1261), and strengthened LPS (routine LPS+ im P 40 mg daily) was administered to group A (P < 10.0 ng/ml on the FET day, n = 1295). The primary endpoint was the live birth rate, and the secondary endpoints were clinical pregnancy, miscarriage and neonatal outcomes.

Results: The results showed that the clinical pregnancy rate was significantly lower in group A than in group B (48.4% vs 53.2%, adjusted risk ratio (aRR) 0.81, 95% confidence interval (CI) 0.68, 0.96), whereas miscarriage rates were similar between the two groups (16.0% vs 14.7%, aRR 1.09, 95% CI 0.77, 1.54). The live birth rate was slightly lower in group A than in group B (39.5% vs 43.3%, aRR 0.84, 95% CI 0.70, 1.0). Birthweights and other neonatal outcomes were similar between the two groups (P > 0.05).

Conclusions: The results indicated that the serum progesterone level on the FET day was one of the risk factors predicting the chances of pregnancy in artificial endometrium preparation cycles, and strengthened LPS in patients with low progesterone on the FET day might help to provide a reasonable pregnancy outcome in artificial cycles, although further prospective evidence is needed to confirm this possibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12958-021-00747-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063468PMC
April 2021

Removal of antibiotic resistance genes from secondary effluent by processes combining nano-iron, ultrasound-activated persulfate, and ultrafiltration.

Water Sci Technol 2021 Apr;83(7):1578-1590

Key Laboratory of Urban Stormwater System and Water Environment, Ministry of Education, Beijing University of Civil Engineering and Architecture, Beijing 100044, China E-mail:

Antibiotic resistance genes (ARGs), as a new type of environmental pollutant that threaten human health, have been detected in the effluent of sewage treatment systems. In this study, the removal from water of ARGs, 16S rRNA, class 1 integron (intI1), and dissolved organic carbon (DOC) were investigated using processes combining nano-iron (nFe), ultrasound (US), activated persulfate (PS) and ultrafiltration (UF). The oxidation mechanism was also studied. The results showed that both nFe and US activation could improve the oxidative effect of PS, and the effect of nFe was better than that of US. Compared with PS-UF, nFe/PS-UF and US/PS-UF significantly enhanced the removal of various ARGs and DOC. nFe/PS-UF was the most effective treatment, reducing cell-associated and cell-free ARGs by 1.74-3.14-log and 1.00-2.61-log, respectively, while removing 30% of DOC. Pre-oxidation methods using PS, nFe/PS, and US/PS significantly enhanced the efficacy of UF for removing DOC with molecular weights above 50 kDa and below 10 kDa, but the removal of DOC between 10 and 50 kDa decreased. The free radicals SO and ·OH were shown to participate in the process of ARGs oxidation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2166/wst.2021.088DOI Listing
April 2021

Brain Basis of Psychopathy in Criminal Offenders and General Population.

Cereb Cortex 2021 Apr 9. Epub 2021 Apr 9.

Department of Clinical Neuroscience, Karolinska Institutet and Center for Psychiatry Research, Stockholm City Council, Stockholm SE-11364, Sweden.

Psychopathy is characterized by persistent antisocial behavior, impaired empathy, and egotistical traits. These traits vary also in normally functioning individuals. Here, we tested whether such antisocial personalities are associated with similar structural and neural alterations as those observed in criminal psychopathy. Subjects were 100 non-convicted well-functioning individuals, 19 violent male offenders, and 19 matched controls. Subjects underwent T1-weighted magnetic resonance imaging and viewed movie clips with varying violent content during functional magnetic resonance imaging. Psychopathic traits were evaluated with Levenson Self-Report Psychopathy Scale (controls) and Psychopathy Checklist-Revised (offenders). Psychopathic offenders had lower gray matter density (GMD) in orbitofrontal cortex and anterior insula. In the community sample, affective psychopathy traits were associated with lower GMD in the same areas. Viewing violence increased brain activity in periaqueductal grey matter, thalamus, somatosensory, premotor, and temporal cortices. Psychopathic offenders had increased responses to violence in thalamus and orbitofrontal, insular, and cingulate cortices. In the community sample, impulsivity-related psychopathy traits were positively associated with violence-elicited responses in similar areas. We conclude that brain characteristics underlying psychopathic spectrum in violent psychopathy are related to those observed in well-functioning individuals with asocial personality features.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cercor/bhab072DOI Listing
April 2021

Interleukin (IL)-1 family cytokines could differentiate primary immune thrombocytopenia from systemic lupus erythematosus-associated thrombocytopenia.

Ann Transl Med 2021 Feb;9(3):222

Department of Hematology, Zhongshan Hospital Fudan University, Shanghai, China.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune-mediated disorder characterized by a decreased platelet count. Systemic lupus erythematosus (SLE) is also an autoimmune disease in which thrombocytopenia is a common hematologic manifestation. Interleukin (IL)-1 family cytokines are major proinflammatory and immunoregulatory mediators. This study aimed to investigate the role of IL-1 cytokines in patients with ITP and SLE and the potential pathophysiologic mechanism to differentiate SLE-associated thrombocytopenia (SLE-TP) from ITP.

Methods: Multiplex cytokine assay and real-time polymerase chain reaction (RT-PCR) were used to measure IL-1 cytokines in 17 newly diagnosed ITP patients, 17 SLE-TP patients, 19 SLE patients without thrombocytopenia (SLE-NTP), and 10 healthy controls.

Results: The serum levels of IL-1β, IL-18, IL-36α, IL-36β, IL-36γ, and IL-33 were decreased significantly in ITP patients compared with SLE-TP patients, SLE-NTP patients, and healthy controls (P<0.05). While there was no significant difference in the serum level of IL-37 between ITP and SLE-TP patients, there was a positive correlation between the platelet count and IL-37 level in ITP patients. Our data suggested that serum IL-1β, IL-18, IL-36α, IL-36β, IL-36γ, IL-33, and IL-37 could be considered biomarkers in the diagnosis of ITP.

Conclusions: Serum IL-1β, IL-18, IL-36α, IL-36β, IL-36γ, and IL-33 could be considered biomarkers to differentiate SLE-TP from ITP patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-4729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940935PMC
February 2021

Fuyuan Xingnao Decoction Promotes Angiogenesis Through the Rab1/AT1R Pathway in Diabetes Mellitus Complicated With Cerebral Infarction.

Front Pharmacol 2021 17;12:616165. Epub 2021 Feb 17.

Department of Emergency Medicine, LongHua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Fuyuan Xingnao decoction (FYXN), a traditional Chinese formula comprised of seven herbs, has been utilized to treat diabetes mellitus complicated with cerebral infarction (DMCI) for years. Yet, its protective and regulatory mechanism is poorly understood. The aim of the study is to investigate the effects of FYXN on DMCI and , as well as its mechanism in angiogenesis. For experiments, FYXN was administered to DMCI rats with streptozotocin (STZ) injection-induced diabetes. Then middle cerebral artery occlusion (MCAO) was conducted and the cerebral cortex sections of the rats were obtained. The ultrastructure of cerebral microvessels and new vessel density of ischemic penumbra were evaluated by the transmission electron microscopy (TEM) assay and immunohistochemistry, respectively. Protein and mRNA expression levels of Rab1/AT1R in cortex were assayed by Western blotting and real-time fluorescence quantitative real-time polymerase chain reaction (RT-qPCR). , FYXN serum was produced in rats on the fourth day 2 h after the last FYXN administration. Green fluorescence was observed after transfection with lentivirus packaged Rab1-WT or siRNA for 24 h. The activity of brain microvascular endothelial cells (BMECs) treated with sera from these rats was tested by MTT assay and Transwell assays, respectively. The expression of AT1R on the cell membrane and endoplasmic reticulum of BMECs was evaluated by immunofluorescence staining. Protein expression levels of signaling molecules in the Rab1/AT1R pathways were also detected. Results showed that , FYXN treatment significantly intensified CD31 staining in the cortical areas and enhanced the mRNA and protein levels of AT1R, Ang II, Rab1a, Rab1b and VEGF expression in ischemic cerebral cortex tissues. , the expression levels of AT1R, Ang II, Rab1a, Rab1b and VEGF in the cerebral infarction model group were significantly higher than those in the control group, with further increases after administration of FYXN drug serum. FYXN promoted the proliferation and migration of BMECs by activating the Rab1/AT1R signaling pathway. In conclusion, FYXN exerts a protective effect against DMCI by promoting angiogenesis via the Rab1/AT1R pathway, which provides strong evidence for the therapeutic effect of FYXN on DMCI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2021.616165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925884PMC
February 2021

A systematic review and meta-regression of studies eliciting willingness-to-pay per quality-adjusted life year in the general population.

Expert Rev Pharmacoecon Outcomes Res 2021 Feb 1:1-9. Epub 2021 Feb 1.

School of business administration, Shenyang Pharmaceutical University, Shenyang, China.

Objectives: From the demand-side perspective, the monetary value of one additional quality-adjusted life year (QALY) is estimated as willingness-to-pay per QALY (WTPQ). This study aims to summarize the methods and contexts of elicitation of willingness-to-pay per quality-adjusted life year (WTPQ) in the general population and to investigate the heterogeneity of WTPQ estimates.

Methods: Meta-regression analysis was conducted using Comprehensive Meta-Analysis Software. Sensitivity analyses were undertaken by replacing the lowest and highest 5% and 2.5% of WTPQ by percentiles.

Results: 33 studies with 102 WTPQ estimates were included. The overall mean and median WTPQ estimates are $1,280,002 and $44,072, respectively. The meta-regressions demonstrated that types of health gain (quality of life or life length) and certainty of health outcomes are statistically significant factors. Furthermore, compared with online interviews, face-to-face interviews tend to yield lower WTPQ. Moreover, the declining trend of QALY gains and positive effect with statistical significance of the sample age were also noticed.

Conclusion: For valid and representative values of WTPQ, future researchers should therefore take into consideration various scenarios and investigate both health gain with certainty and uncertainty, health gain from both life length and quality of life, and different size of QALY gains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14737167.2021.1878881DOI Listing
February 2021

Treatment of Aggressive T Cell Lymphoblastic Lymphoma/leukemia Using Anti-CD5 CAR T Cells.

Stem Cell Rev Rep 2021 Apr 6;17(2):652-661. Epub 2021 Jan 6.

Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, People's Republic of China.

While treatment for B-cell malignancies has been revolutionized through the advent of CAR immunotherapy, similar strategies for T-cell malignancies have been limited. Additionally, T-cell leukemias and lymphomas can commonly metastasize to the CNS, where outcomes are poor and treatment options are associated with severe side effects. Consequently, the development of safer and more effective alternatives for targeting malignant T cells that have invaded the CNS remains clinically important. CD5 CAR has previously been shown to effectively target various T-cell cancers in preclinical studies. As IL-15 strengthens the anti-tumor response, we have modified CD5 CAR to secrete an IL-15/IL-15sushi complex. In a Phase I clinical trial, these CD5-IL15/IL15sushi CAR T cells were tested for safety and efficacy in a patient with refractory T-LBL with CNS infiltration. CD5-IL15/IL15sushi CAR T cells were able to rapidly ablate the CNS lymphoblasts within a few weeks, resulting in the remission of the patient's lymphoma. Despite the presence of CD5 on normal T cells, the patient only experienced a brief, transient T-cell aplasia. These results suggest that CD5-IL15/IL15sushi CAR T cells may be a safe and useful treatment of T-cell malignancies and may be particularly beneficial for patients with CNS involvement.Graphical Abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12015-020-10092-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036178PMC
April 2021

Decoding Music-Evoked Emotions in the Auditory and Motor Cortex.

Cereb Cortex 2021 Mar;31(5):2549-2560

Turku PET Centre, and Turku University Hospital, University of Turku, 20520, Turku, Finland.

Music can induce strong subjective experience of emotions, but it is debated whether these responses engage the same neural circuits as emotions elicited by biologically significant events. We examined the functional neural basis of music-induced emotions in a large sample (n = 102) of subjects who listened to emotionally engaging (happy, sad, fearful, and tender) pieces of instrumental music while their hemodynamic brain activity was measured with functional magnetic resonance imaging (fMRI). Ratings of the four categorical emotions and liking were used to predict hemodynamic responses in general linear model (GLM) analysis of the fMRI data. Multivariate pattern analysis (MVPA) was used to reveal discrete neural signatures of the four categories of music-induced emotions. To map neural circuits governing non-musical emotions, the subjects were scanned while viewing short emotionally evocative film clips. The GLM revealed that most emotions were associated with activity in the auditory, somatosensory, and motor cortices, cingulate gyrus, insula, and precuneus. Fear and liking also engaged the amygdala. In contrast, the film clips strongly activated limbic and cortical regions implicated in emotional processing. MVPA revealed that activity in the auditory cortex and primary motor cortices reliably discriminated the emotion categories. Our results indicate that different music-induced basic emotions have distinct representations in regions supporting auditory processing, motor control, and interoception but do not strongly rely on limbic and medial prefrontal regions critical for emotions with survival value.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cercor/bhaa373DOI Listing
March 2021

Seasonal Variation in the Brain μ-Opioid Receptor Availability.

J Neurosci 2021 02 23;41(6):1265-1273. Epub 2020 Dec 23.

Turku PET Centre, University of Turku, FIN-20520 Turku, Finland.

Seasonal rhythms influence mood and sociability. The brain μ-opioid receptor (MOR) system modulates a multitude of seasonally varying socioemotional functions, but its seasonal variation remains elusive with no previously reported evidence. Here, we first conducted a cross-sectional study with previously acquired human [C]carfentanil PET imaging data (132 male and 72 female healthy subjects) to test whether there is seasonal variation in MOR availability. We then investigated experimentally whether seasonal variation in daylength causally influences brain MOR availability in rats. Rats (six male and three female rats) underwent daylength cycle simulating seasonal changes; control animals (two male and one female rats) were kept under constant daylength. Animals were scanned repeatedly with [C]carfentanil PET imaging. Seasonally varying daylength had an inverted U-shaped functional relationship with brain MOR availability in humans. Brain regions sensitive to daylength spanned the socioemotional brain circuits, where MOR availability peaked during spring. In rats, MOR availabilities in the brain neocortex, thalamus, and striatum peaked at intermediate daylength. Varying daylength also affected the weight gain and stress hormone levels. We conclude that cerebral MOR availability in humans and rats shows significant seasonal variation, which is predominately associated with seasonal photoperiodic variation. Given the intimate links between MOR signaling and socioemotional behavior, these results suggest that the MOR system might underlie seasonal variation in human mood and social behavior. Seasonal rhythms influence emotion and sociability. The central μ-opioid receptor (MOR) system modulates numerous seasonally varying socioemotional functions, but its seasonal variation remains elusive. Here we used positron emission tomography to show that MOR levels in both human and rat brains show daylength-dependent seasonal variation. The highest MOR availability was observed at intermediate daylengths. Given the intimate links between MOR signaling and socioemotional behavior, these results suggest that the MOR system might underlie seasonal variation in human mood and social behavior.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.2380-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7888218PMC
February 2021

A comparison of the accuracy of the CapitalBio Mycobacterium real-time polymerase chain reaction and the Xpert MTB/RIF assay for the diagnosis of tuberculous meningitis.

Int J Infect Dis 2021 Mar 19;104:92-96. Epub 2020 Dec 19.

Zhejiang Tuberculosis Diagnosis and Treatment Center, Zhejiang Chinese Medicine and Western Medicine Integrated Hospital, Hangzhou, Zhejiang, China. Electronic address:

Objectives: We aimed to compare the efficiency of the CapitalBioMycobacterium real-time polymerase chain reaction (PCR) detection test with the standard Xpert MTB/RIF assay for the diagnosis of tuberculous meningitis (TBM).

Methods: We analyzed cerebrospinal fluid (CSF) from 163 patients with suspected TBM that were collected between January 1, 2018, and December 31, 2019. For both tests, we determined the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC). Next, we compared the diagnostic accuracy of the two techniques using clinical diagnosis as a reference standard.

Results: The sensitivity, specificity, PPV, NPV, and AUC, of the CapitalBio Mycobacterium detection test were 48.5%, 100%, 100%, 29.6%, and 0.74, respectively, when used for the diagnosis of TBM. In comparison, the Xpert MTB/RIF assay returned values of 47.0%, 100%, 100%, 29.0%, and 0.74, respectively. Our analysis showed that the diagnostic accuracies of the CapitalBio Mycobacterium detection test and the Xpert MTB/RIF assay were very similar; the accuracy of both tests for detecting mycobacteria was significantly higher than that associated with acid-fast staining.

Conclusions: The CapitalBio Mycobacterium real-time PCR detection test has moderate sensitivity and very high specificity for TBM; results are very similar to those generated by the Xpert MTB/RIF assay. We recommend that the CapitalBio PCR test should be used as an initial screening method for TB.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijid.2020.12.044DOI Listing
March 2021

Inhalation of low-dose desflurane prevents the hemodynamic instability caused by target-controlled infusion of remifentanil and propofol during laparoscopic gynecological surgery: A randomized controlled trial.

Exp Ther Med 2021 Jan 19;21(1):54. Epub 2020 Nov 19.

Department of Anesthesiology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.

The objective of the present study was to determine whether the addition of inhaled desflurane is superior to remifentanil-propofol total intravenous anesthesia (TIVA) alone in patients undergoing laparoscopic gynecological surgery. A total of 60 patients who were scheduled to undergo laparoscopic gynecological surgery were prospectively enrolled and randomly allocated to receive either propofol-remifentanil (PR group; n=30) or combined propofol-remifentanil and low-dose desflurane (PRD group; n=30) for the maintenance of anesthesia. Hemodynamics [mean arterial pressure (MAP); heart rate (HR)], recovery parameters and complications were recorded. The results of the present study indicated that the addition of desflurane significantly reduced the amount of propofol and remifentanil that was administered in the PRD group, compared with that in the PR group. MAP and HR were significantly higher at T3 (5 min post-pneumoperitoneum), but significantly lower at T4 (removal of pneumoperitoneum needle) and T5 (post-operation immediately) in the PR group, compared with the PRD group. Moreover, MAP and HR were significantly altered at multiple time points within the PR group; however, they were relatively stable in the PRD group. There were no significant differences in the recovery parameters and complications between the two groups. In conclusion, combining low-dose desflurane with PR may represent an efficient anesthesia regimen to prevent the hemodynamic instability of TIVA in patients undergoing laparoscopic gynecological surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2020.9486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7706382PMC
January 2021

Commentary: Time perception deficits and its dose-dependent effect in methamphetamine dependents with short-term abstinence.

Front Cell Neurosci 2020 8;14:263. Epub 2020 Sep 8.

Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University, Changchun, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fncel.2020.00263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7507969PMC
September 2020

Atorvastatin improves the proliferation and migration of endothelial progenitor cells via the miR-221/VEGFA axis.

Biosci Rep 2020 11;40(11)

Department of Cardiology, Fifth Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China.

The present study was aimed at investigating the detailed functions of atorvastatin, a lipid-lowering agent, in the pathogenesis of coronary slow flow (CSF), a clinical disease characterized by delayed angiographic coronary opacity without obstructive coronary disease. In the present study, we successfully identified isolated endothelial progenitor cells (EPCs) from the peripheral blood of patients with CSF. Their vascular endothelial growth factor-A (VEGFA) protein levels were determined using immunoblotting analyses. We determined cell viability using MTT assays, cell migration capacity using Transwell assays, and the angiogenic capacity using a tube formation assay. The target association between miR-221 and VEGFA was validated with a luciferase reporter assay. Atorvastatin treatment increased EPC VEGFA protein levels, proliferation, migration, and angiogenesis. miR-221 expression was down-regulated after atorvastatin treatment; miR-221 overexpression exerted an opposing effect to atorvastatin treatment on VEGFA protein, EPC proliferation, migration, and angiogenesis. The protective effects of atorvastatin treatment on VEGFA protein and EPCs could be significantly suppressed by miR-221 overexpression. miR-221 directly bound the VEGFA 3'UTR to inhibit its expression. In conclusion, atorvastatin improves the cell proliferation, migration, and angiogenesis of EPCs via the miR-221/VEGFA axis. Thus, atorvastatin could be a potent agent against CSF, pending further in vivo and clinical investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1042/BSR20193053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689653PMC
November 2020

Protein synthesis is suppressed in sporadic and familial Parkinson's disease by LRRK2.

FASEB J 2020 11 14;34(11):14217-14233. Epub 2020 Sep 14.

Turku Bioscience, University of Turku and Åbo Akademi University, Turku, Finland.

Gain of function LRRK2-G2019S is the most frequent mutation found in familial and sporadic Parkinson's disease. It is expected therefore that understanding the cellular function of LRRK2 will provide insight on the pathological mechanism not only of inherited Parkinson's, but also of sporadic Parkinson's, the more common form. Here, we show that constitutive LRRK2 activity controls nascent protein synthesis in rodent neurons. Specifically, pharmacological inhibition of LRRK2, Lrrk2 knockdown or Lrrk2 knockout, all lead to increased translation. In the rotenone model for sporadic Parkinson's, LRRK2 activity increases, dopaminergic neuron translation decreases, and the neurites atrophy. All are prevented by LRRK2 inhibitors. Moreover, in striatum and substantia nigra of rotenone treated rats, phosphorylation changes are observed on eIF2α-S52(↑), eIF2s2-S2(↓), and eEF2-T57(↑) in directions that signify protein synthesis arrest. Significantly, translation is reduced by 40% in fibroblasts from Parkinson's patients (G2019S and sporadic cases alike) and this is reversed upon LRRK2 inhibitor treatment. In cells from multiple system atrophy patients, translation is unchanged suggesting that repression of translation is specific to Parkinson's disease. These findings indicate that repression of translation is a proximal function of LRRK2 in Parkinson's pathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1096/fj.202001046RDOI Listing
November 2020

GDF11 replenishment protects against hypoxia-mediated apoptosis in cardiomyocytes by regulating autophagy.

Eur J Pharmacol 2020 Oct 28;885:173495. Epub 2020 Aug 28.

Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, 150081, PR China; Department of Pharmacology and Therapeutics, Melbourne School of Biomedical Sciences, Faculty of Medicine, Dentistry and HealthSciences University of Melbourne, Melbourne VIC, 3010, Australia.

GDF11 has been reported to play a critical role in rejuvenating hypertrophy heart, skeletal muscle, and blood vessel regeneration in aged mice. Whether GDF11 can regulate autophagy in cardiomyocytes remains largely unknown. Thus, the purpose of the present study was to investigate the effects of GDF11 on cardiomyocyte autophagy induced by hypoxia, in addition to the underlying mechanisms. By using the MTT assay, Flow cytometry assay, LIVE/DEAD® Viability/Cytotoxicity Kit Stains and TUNEL assay, we found that exogenous GDF11 decreased apoptosis caused by prolonged hypoxia in cardiomyocytes. The expression of GDF11 was decreased obviously both in the cardiac tissue of myocardial infarction mice and the hypoxia treated cardiomyocytes. Protein levels of cleaved caspase-3, p-AMPK, SQSTM1, LC3B-I/II and GDF11 were detected by western blot. Autophagosomes and autolysosomes were identified by confocal laser microscopy after transfecting with the mRFP-eGFP-LC3 plasmids. Antibody against GDF11 (anti-GDF11) was used to inhibit the function of GDF11. At the molecular level, exogenous GDF11 increased AMPK function and enhanced autophagy activity. Anti-GDF11 inhibited autophagy and aggravated hypoxia-induced apoptosis in cardiomyocytes. Thus, GDF11 might be a potential target for myocardial infarction therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejphar.2020.173495DOI Listing
October 2020

Progress in Vaccination of Prophylactic Human Papillomavirus Vaccine.

Front Immunol 2020 10;11:1434. Epub 2020 Jul 10.

Department of Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun, China.

The human papillomavirus (HPV) vaccine plays an important role in preventing a series of diseases caused by HPV. Recent studies have shown that as a primary prevention measure, it can considerably prevent HPV infection and HPV-associated cervical cancer. However, studies on the safety, efficacy, and coverage of the HPV vaccine remain insufficient, especially in developing countries. Therefore, in this review, we outlined the recent studies of the HPV vaccine in terms of immunogenicity, safety, efficacy, latest vaccination concepts, and strategies. This review may provide a theoretical basis for use of the HPV vaccine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.01434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365840PMC
April 2021

SCFAs induce autophagy in intestinal epithelial cells and relieve colitis by stabilizing HIF-1α.

J Mol Med (Berl) 2020 08 22;98(8):1189-1202. Epub 2020 Jul 22.

Department of General Surgery, Xinqiao Hospital, Army Medical University, Chongqing, China.

Hypoxia-inducible factor-1α (HIF-1α) is a critical regulator of barrier integrity during colonic mucosal injury. Previous works have shown that the absence of autophagy is implicated in the development of inflammatory bowel disease (IBD). Additionally, changes in bacterial profiles in the gut are intimately associated with IBD. Although HIF-1α, autophagy, microbiota, and their metabolites are all involved in the pathogenesis of IBD, their roles are not known. In this study, we investigated the relationship between HIF-1α and autophagy in healthy and inflammatory states using transgenic mice, colitis models, and cell culture models. We confirmed that the absence of intestinal epithelial HIF-1α changed the composition of the intestinal microbes and increased the susceptibility of mice to dextran sodium sulfate (DSS)-induced colitis. In addition, autophagy levels in the intestinal epithelial cells (IECs) were significantly reduced in IEC-specific HIF-1α-deficient (HIF-1α) mice. Moreover, in the cell culture models, butyrate treatment significantly increased autophagy in HT29 cells under normal conditions, whereas butyrate had little effect on autophagy after HIF-1α ablation. Furthermore, in the DSS-induced colitis model, butyrate administration relieved the colonic injury and suppressed inflammation in Cre-/HIF-1α- (HIF-1α) mice. However, the butyrate-mediated protection against colonic injury was considerably diminished in the HIF-1α mice. These results show that HIF-1α, autophagy, and intestinal microbes are essential for the maintenance of intestinal homeostasis. Butyrate can alleviate DSS-induced colitis by regulating autophagy via HIF-1α. These insights may have important implications for the development of therapeutic strategies for IBD. KEY MESSAGES: • The absence of intestinal epithelial HIF-1α leads to downregulation of autophagy in mice. • The absence of intestinal epithelial HIF-1α exacerbates DSS-induced colitis. • Short-chain fatty acids (SCFAs) can alleviate DSS-induced colitis by regulating autophagy via HIF-1α.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00109-020-01947-2DOI Listing
August 2020

Biallelic mutations in CDC20 cause female infertility characterized by abnormalities in oocyte maturation and early embryonic development.

Protein Cell 2020 12;11(12):921-927

Institute of Pediatrics, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and metabolism, Ministry of Science and technology and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13238-020-00756-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719138PMC
December 2020

Circulating CX3CR1CD163 M2 monocytes markedly elevated and correlated with cardiac markers in patients with acute myocardial infarction.

Ann Transl Med 2020 May;8(9):578

Department of Thoracic Surgery, Zhongshan Hospital Xuhui Branch, Fudan University, Shanghai 200031, China.

Background: Vulnerable plaques have been generally recognized to play a role in the pathogenesis of acute myocardial infarction (AMI), however, the role of circulating CX3CR1CD163 M2 monocytes has not been studied properly. We aim to evaluate the features of CX3CR1CD163 M2 monocytes and its relationship with cardiac specific markers in AMI patients.

Methods: The circulating M2 monocytes were identified in AMI patients (n=35) and healthy controls (HCs, n=10) by flow cytometry using two staining methods: CD68CD163 (cytoplasmic staining) and CX3CR1CD163 (surface staining). CX3CR1 monocytes were purified by magnetic cell sorting. The expression level of peroxisome proliferator-activated receptor γ (PPARγ) and arginase-1 (Arg-1) were measured by real-time quantitative PCR and Western Blot in CX3CR1 monocytes.

Results: Circulating M2 monocytes extremely expanded in AMI patients compared with HCs (P<0.01). Positive linear correlation was confirmed between CD68CD163 and CX3CR1CD163 cell populations in AMI patients (r=0.39, P=0.02). The percentage of circulating CX3CR1CD163 M2 monocytes positively correlated with cardiac specific markers (cTNT, CK-MB) and acute phase markers (glucose, hs-CRP) (cTNT, r=0.63, P<0.01, CK-MB, r=0.54, P<0.01, glucose, r=0.62, P<0.01, hs-CRP, r=0.58, P<0.01). CX3CR1 monocytes in AMI patients expressed higher levels of PPARγ and Arg-1 than those in HCs (P<0.01).

Conclusions: Circulating M2 monocytes increased in AMI patients and positively correlated with the elevation of both cardiac specific and acute phase markers. CX3CR1CD163 M2 monocytes might have application value for the early diagnosis of AMI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290533PMC
May 2020

Predicting the emission characteristics of VOCs in a simulated vehicle cabin environment based on small-scale chamber tests: Parameter determination and validation.

Environ Int 2020 09 7;142:105817. Epub 2020 Jun 7.

School of Mechanical Engineering, Beijing Institute of Technology, Beijing 100081, China. Electronic address:

Volatile organic compounds (VOCs) emitted from vehicle parts and interior materials can seriously affect in-cabin air quality. Prior studies mainly focused on indoor material emissions, while studies of emissions in-cabins were relatively scarce. The emission behaviors of VOCs from vehicle cabin materials can be characterized by three key emission parameters: the initial emittable concentration (C), diffusion coefficient (D), and partition coefficient (K). Based on a C-history method, we have performed a series of tests with a 30 L small-scale chamber to determine these three key emission parameters for six VOCs, benzene, toluene, ethylbenzene, xylene, formaldehyde, and acetaldehyde, from typical vehicle cabin materials, car roof upholstery, carpet, and seat. We found that acetaldehyde had the highest level in the gas-phase concentration and C, which differs from residential indoor environments where formaldehyde is usually the most prevalent pollutant. The influence of temperature on the key emission parameters was also investigated. When the temperature rose from 25 °C to 65 °C, C increased by 40-640%, D increased by 40-170%, but K decreased by 38-71% for different material-VOC combinations. We then performed an independent validation to demonstrate the accuracy of the measured key emission parameters. Furthermore, considering that in reality, several materials coexist in vehicle cabins, we made a first attempt at applying a multi-source model to predict VOC emission behaviors in a simulated 3 m vehicle cabin, using the key emission parameters obtained from the small-scale chamber tests. The good agreement between the predictions and experiments (R = 0.82-0.99) demonstrated that the three key emission parameters measured via chamber tests can be scaled to estimate emission scenarios in realistic vehicle cabin environments. A pollution contribution analysis for the tested materials indicated that the car seat could significantly contribute to the total emissions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2020.105817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485589PMC
September 2020

Up-regulation of miR-195 contributes to cardiac hypertrophy-induced arrhythmia by targeting calcium and potassium channels.

J Cell Mol Med 2020 07 28;24(14):7991-8005. Epub 2020 May 28.

Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang, China.

Previous studies have confirmed that miR-195 expression is increased in cardiac hypertrophy, and the bioinformatics website predicted by Targetscan software shows that miR-195 can directly target CACNB1, KCNJ2 and KCND3 to regulate Cavβ1, Kir2.1 and Kv4.3 proteins expression. The purpose of this study is to confirm the role of miR-195 in arrhythmia caused by cardiac hypertrophy. The protein levels of Cavβ1, Kir2.1 and Kv4.3 in myocardium of HF mice were decreased. After miR-195 was overexpressed in neonatal mice cardiomyocytes, the expression of ANP, BNP and β-MHC was up-regulated, and miR-195 inhibitor reversed this phenomenon. Overexpression of miR-195 reduced the estimated cardiac function of EF% and FS% in wild-type (WT) mice. Transmission electron microscopy showed that the ultrastructure of cardiac tissues was damaged after miR-195 overexpression by lentivirus in mice. miR-195 overexpression increased the likelihood of arrhythmia induction and duration of arrhythmia in WT mice. Lenti-miR-195 inhibitor carried by lentivirus can reverse the decreased EF% and FS%, the increased incidence of arrhythmia and prolonged duration of arrhythmia induced by TAC in mice. After miR-195 treatment, the protein expressions of Cavβ1, Kir2.1 and Kv4.3 were decreased in mice. The results were consistent at animal and cellular levels, respectively. Luciferase assay results showed that miR-195 may directly target CACNB1, KCNJ2 and KCND3 to regulate the expression of Cavβ1, Kir2.1 and Kv4.3 proteins. MiR-195 is involved in arrhythmia caused by cardiac hypertrophy by inhibiting Cavβ1, Kir2.1 and Kv4.3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.15431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348160PMC
July 2020

LINC00174 is a favorable prognostic biomarker in glioblastoma via promoting proliferative phenotype.

Cancer Biomark 2020 ;28(4):421-427

Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Objective: To investigate the expression pattern, prognostic value and biological functional of LINC00174 in glioma.

Methods: In total, 140 glioma samples were collected as discovery cohort. TCGA RNA sequence dataset was obtained as validation set. Kaplan-Meier survival and multivariate Cox analysis were performed to evaluate survival difference. Furthermore, the biological function of LINC00174 was analyzed by clonogenic and intracranial tumor model assays.

Results: Overexpressed LINC00174 was significantly correlated with tumor grade as well as the higher mortality in survival analysis both in the discovery and the validation GBM cohorts. Besides, LINC00174 served as an independent prognostic indicator in glioblastoma patients. Additionally, knock down of LINC00174 expression significantly suppressed GBM cells' proliferation both in vitro and vivo.

Conclusion: LINC00174 acts as an oncogene in glioma and may be a new potential therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3233/CBM-191026DOI Listing
April 2021

Decreased Plasma Maresin 1 Concentration Is Associated with Diabetic Foot Ulcer.

Mediators Inflamm 2020 16;2020:4539035. Epub 2020 Apr 16.

Department of Endocrinology, Translational Research of Diabetes Key Laboratory of Chongqing Education Commission of China, The Second Affiliated Hospital of Army Medical University, Chongqing, China.

Aims: To assess the maresin 1 (MaR1) contents in type 2 diabetic patients with or without diabetic foot ulcer and to analyze the association of MaR1 concentrations with several metabolism-related parameters.

Methods: Plasma MaR1 concentrations were analyzed in 96 subjects with normal glucose tolerant (NC, = 43), type 2 diabetes (T2DM, = 40), or diabetic foot ulcer (DFU, = 13). The intravenous glucose tolerance test (IVGTT) and biochemical parameters were measured in all participants.

Results: Plasma MaR1 concentrations were significant decreased in type 2 diabetes patient with or without DFU compared with NC (both < 0.001) and were lowest in DFU patients among these 3 groups. (DFU vs. T2DM, < 0.05). Plasma MaR1 concentrations were negatively correlated with BMI, waist circumference (Wc), waist hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-c, FPG, 2hPG, HbA1c, and homeostasis model assessment for insulin resistance (HOMA-IR) (all < 0.05) and were positively correlated with HDL-c, acute insulin response (AIR), area under the curve of the first-phase (0-10 min) insulin secretion (AUC), and homeostasis model assessment for beta-cell function (HOMA-) (all < 0.05). After adjusting for age and sex, Wc, WHR, TG, FPG, 2hPG, HbA1c, HOMA-IR, AIR, AUC, and HOMA- remain statistically significant (all < 0.05).

Conclusions: Plasma MaR1 concentration were decreased in T2DM with or without DFUs and were the lowest in DFU patients. The decreased plasma MaR1 strongly associated with obesity, impaired glucose and lipid metabolism, reduced first-phase of glucose-stimulated insulin secretion, and enhanced insulin resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/4539035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182968PMC
May 2021

Intestinal microbiota dysbiosis play a role in pathogenesis of patients with primary immune thrombocytopenia.

Thromb Res 2020 06 19;190:11-19. Epub 2020 Mar 19.

Department of Hematology, Zhongshan Hospital Fudan University, Shanghai 200032, China; Department of Hematology, Zhongshan Hospital Qingpu Branch, Fudan University, Shanghai 201700, China; Institute of Clinical Science, Zhongshan Hospital Fudan University, Shanghai 200032, China; Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai 201508, China. Electronic address:

Background: The intestinal microbiota is essential for the maintenance of the physiology of immune homeostasis. Dysbiosis has been described in some autoimmune diseases, however its role is still elusive in primary immune thrombocytopenia (ITP), which is one kind of autoimmune diseases. This study aimed to characterize the phylogenetic diversity of the fecal microbiota and its relationship with the platelet activation status in patients with ITP.

Methods: The platelet activation status was assessed by 2 platelet markers, PAC-1 (antibody that recognizes the activated GPIIb/IIIa complex) and CD62p (Platelet surface P-selectin) by flow cytometry. Total DNA was extracted from fecal samples of ITP patients and healthy controls (HC). Sequencing the V4 hypervariable region of bacterial 16S rRNA genes was used to identify the changes in phylogenetic diversity and composition of the intestinal flora. The obtained sequencing reads were assigned to operational taxonomic units (OTUs, 97% sequence identity) and taxonomically classified to assess composition and diversity.

Results: The percentage of PAC-1+ platelets in ITP patients was higher than that in control group (p < 0.001), The percentage of CD62p+ and PAC-1+CD62p+ platelets in ITP patients both higher than those in control group (p < 0.001). At the phylum level, eight different phyla were identified in ITP individuals, with a majority of Bacteroidetes (45.96%) and Firmicutes (38.59%), followed by Proteobacteria (11.43%), Fusobacteria(1.29%), and Actinobacteria (1.22%). While in the Healthy volunteers, ten phyla were detected, with a predominance of Firmicutes (50.92%) and Bacteroidetes (34.26%), came before Proteobacteria (13.60%), and Actinobacteria (0.90%). The gut microbiota was skewed in ITP, with an increased proportion of Proteobacteria, Bacteroidetes and Bacteroidetes/Firmicutes ratio, a decreased proportion of Firmicutes compared with HC. Disease specific alterations in diversity was also identified, especially the potential markers (Anaerorhabdus, sutterella, Peptostreptococcaceae, Clostridium_XI and carnobacteriaceae, p < 0.05) for ITP.

Conclusions: The results suggested that the distinct microbiota dysbiosis in ITP characterized by alterations in biodiversity and composition, which could provide insights for diet therapy and fecal microbiota transplantation treatment to cure ITP. There might be somehow compensatory enhancement of platelet activation in ITP patients. And there is associate between platelet activation and intestinal microbiota in patients with ITP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.thromres.2020.03.012DOI Listing
June 2020

A novel homozygous variant in NLRP5 is associate with human early embryonic arrest in a consanguineous Chinese family.

Clin Genet 2020 07 16;98(1):69-73. Epub 2020 Apr 16.

Reproductive Medicine Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Early embryonic arrest is one of the major causes of recurrent assisted reproduction failure. It is characterized by delayed embryonic development and failure to form viable eight-cell stage embryos on day 3 of an assisted reproduction cycle. A recent study reported that biallelic mutations in NLRP5 can cause early embryonic arrest. NLRP5 is a member of subcortical maternal complex, which plays a significant role in embryogenesis. In this study, we described a female in a consanguineous Chinese family who displayed clinical features of early embryonic arrest and identified a novel homozygous variant c.1061C>T (p.Pro354Leu) in NLRP5. This is the second report of the biallelic NLRP5 variant that associates with early embryonic arrest in humans, further confirming the role of NLRP5 variants in early embryonic arrest and expanding the spectrum of known pathogenic variants in NLRP5.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cge.13744DOI Listing
July 2020