Publications by authors named "Fangfang Sun"

123 Publications

Social media for pupils: Evolution of podcasts in ophthalmology.

Clin Exp Ophthalmol 2022 Jun 28. Epub 2022 Jun 28.

Faculty of Medicine, McGill University, Montréal, QC, Canada.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ceo.14130DOI Listing
June 2022

Impact of in vitro fertilization-embryo transfer on mother-to-infant transmission in women with chronic HBV infection.

Liver Int 2022 Jun 27. Epub 2022 Jun 27.

Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Background And Aims: In vitro fertilization-embryo transfer (IVF-ET) may increase the risk of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). The purpose of this study was to investigate the impact and safety of IVF-ET on MTCT in women with chronic HBV infection (CHB).

Methods: The data of 298 women who got pregnant by IVF-ET and their 375 children were collected retrospectively. Mothers were divided into the CHB group (n = 224) and the control group (HBsAg negative, n = 74). After birth, newborns were routinely vaccinated with the hepatitis B vaccine, and infants in the CHB group were injected with hepatitis B immunoglobulin within 2 h after birth. Demographic information, clinical data and laboratory test results were collected. The primary outcome measures were the MTCT rate of HBV, and the secondary outcome measures were the safety of the mother and infant.

Results: There was no case of HBV MTCT in all 282 newborns born in the CHB group and 93 neonates born in the control group. Of the two groups, the birth weight (3056.74 ± 601.65 vs. 2926.24 ± 704.86, P = .083), length (49.22 ± 1.97 vs. 48.74 ± 3.09, P = .167), 5-min Apgar score (9.97 ± 0.21 vs. 9.90 ± 0.51, P = .212), days of pregnancy (265.70 ± 12.73 vs. 262.02 ± 17.50, P = .064) and neonatal malformation rate (0.71% vs. 0, P = 1.000) were similar. Two cases of neonatal malformation occurred in the CHB group. The incidences of pregnancy and childbirth complications were similar between the two groups.

Conclusion: IVF-ET does not increase the risk of MTCT in women with chronic HBV infection, and it is safe for mothers and infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.15349DOI Listing
June 2022

Cascade nanozymes based on the "butterfly effect" for enhanced starvation therapy through the regulation of autophagy.

Biomater Sci 2022 Jun 21. Epub 2022 Jun 21.

School of Pharmaceutical Science, Zhengzhou University, Zhengzhou 450001, China.

Although tumor starvation therapy has been proven to be an excellent method for tumor therapy, its efficiency may be weakened by autophagy, a self-protection mechanism exerted by tumors under starvation stress. Interestingly, over-activated autophagy not only improves the efficacy of starvation therapy, but also induces autophagic death. Herein, we report cascade nanozymes for enhanced starvation therapy by inducing over-activated autophagy. First, glucose oxidase (GOx) modified metal-organic frameworks (NH-MIL88, MOF) were constructed (MOF-GOx). After loading with curcumin (Cur), [email protected] was further decorated with tumor-targeting hyaluronic acid (HA) to obtain [email protected]/HA nanozymes. GOx can catalyze glucose into HO and gluconic acid, which not only leads to tumor starvation, but also provides reactants for the Fenton reaction mediated by the MOF to generate hydroxyl radicals (˙OH) for chemo-dynamic therapy. Most importantly, protective autophagy caused by tumor starvation can be over-activated by Cur to convert autophagy from pro-survival to pro-death, realizing augmented anticancer therapy efficacy. With these cascade reactions, the synergistic action of starvation, autophagy and chemo-dynamic therapy was realized. Generally, the introduction of [email protected]/HA into tumor cells leads to a "butterfly effect", which induces enhanced starvation therapy through subsequent autophagic cell death to completely break the self-protective mechanism of cancer cells, and generate ˙OH for chemo-dynamic therapy. Precise design allows for the use of cascade nanozymes to realize efficient cancer treatment and restrain metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d2bm00595fDOI Listing
June 2022

Case Report: Multimodal Imaging Guides the Management of an Eosinophilic Leukemia Patient With Eosinophilic Myocarditis and Intracardiac Thrombus.

Front Cardiovasc Med 2022 3;9:903323. Epub 2022 Jun 3.

Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, China.

Background: Eosinophilic leukemia (EL) is a rare, serious and potentially life-threatening condition characterized by the overproduction of eosinophils leading to tissue eosinophilic infiltration and damage. Although multiple organ systems may be involved, progressive eosinophilic myocarditis (EM) is the most common cause of morbidity and mortality. Early diagnosis and follow-up surveillance combined with multimodal imaging are crucial for appropriate treatment of EM.

Case Summary: It's a rare case of EL with EM and intracardiac thrombus in a 59-year-old patient who presented with asthenia for 3 weeks. Full blood count analysis indicated significant eosinophilia. Bone marrow aspirate revealed dysplastic eosinophilia and a FIP1L1-PDGFRA fusion gene (4q12) was detected, confirming EL. Echocardiography revealed EM with intracardiac thrombus. This was later confirmed by cardiac magnetic resonance imaging. The patient was commenced on imatinib and prednisolone and good clinical response was obtained. Through 18F-FAPI PET/CT imaging, we obtained visualization of fibroblast activation changes in the early stage of cardiac structure remodeling. With anti-fibrotic therapy after heart failure, the patient achieved a good clinical response.

Conclusion: This case demonstrates visualization of fibroblast activation after EM. Multimodality imaging can provide early diagnosis and may guide tailored antifibrotic therapy in early stage of EM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2022.903323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204136PMC
June 2022

Derivation and Validation of a Screening Model for Hypertrophic Cardiomyopathy Based on Electrocardiogram Features.

Front Cardiovasc Med 2022 24;9:889523. Epub 2022 May 24.

Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.

Background: Hypertrophic cardiomyopathy (HCM) is a widely distributed, but clinically heterogeneous genetic heart disease, affects approximately 20 million people worldwide. Nowadays, HCM is treatable with the advancement of medical interventions. However, due to occult clinical presentations and a lack of easy, inexpensive, and widely popularized screening approaches in the general population, 80-90% HCM patients are not clinically identifiable, which brings certain safety hazards could have been prevented. The majority HCM patients showed abnormal and diverse electrocardiogram (ECG) presentations, it is unclear which ECG parameters are the most efficient for HCM screening.

Objective: We aimed to develop a pragmatic prediction model based on the most common ECG features to screen for HCM.

Methods: Between April 1st and September 30th, 2020, 423 consecutive subjects from the International Cooperation Center for Hypertrophic Cardiomyopathy of Xijing Hospital [172 HCM patients, 251 participants without left ventricular hypertrophy (non-HCM)] were prospectively included in the training cohort. Between January 4th and February 30th, 2021, 163 participants from the same center were included in the temporal internal validation cohort (62 HCM patients, 101 non-HCM participants). External validation was performed using retrospectively collected ECG data from Xijing Hospital (3,232 HCM ECG samples from January 1st, 2000, to March 31st, 2020; 95,184 non-HCM ECG samples from January 1st to December 31st, 2020). The C-statistic was used to measure the discriminative ability of the model.

Results: Among 30 ECG features examined, all except abnormal Q wave significantly differed between the HCM patients and non-HCM comparators. After several independent feature selection approaches and model evaluation, we included only two ECG features, T wave inversion (TWI) and the amplitude of S wave in lead V1 (SV1), in the HCM prediction model. The model showed a clearly useful discriminative performance (C-statistic > 0.75) in the training [C-statistic 0.857 (0.818-0.896)], and temporal validation cohorts [C-statistic 0.871 (0.812-0.930)]. In the external validation cohort, the C-statistic of the model was 0.833 [0.825-0.841]. A browser-based calculator was generated accordingly.

Conclusion: The pragmatic model established using only TWI and SV1 may be helpful for predicting the probability of HCM and shows promise for use in population-based HCM screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2022.889523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170889PMC
May 2022

Effect of Antiviral Therapy During Pregnancy on Natural Killer Cells in Pregnant Women With Chronic HBV Infection.

Front Immunol 2022 23;13:893628. Epub 2022 May 23.

Department of Gynecology and Obstetrics, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Objective: To study the effect of antiviral therapy during pregnancy on the frequency of natural killer (NK) cells in peripheral blood of women with HBV DNA positive chronic hepatitis B (CHB).

Method: In total 124 female subjects were divided into four groups: 11 healthy non-pregnant women (Normal group), 26 non-pregnant women in immune tolerance period of chronic hepatitis B virus (HBV) infection (CHB group), 41 pregnant CHB women without antiviral treatment during pregnancy (Untreated group), and 46 pregnant CHB women receiving antiviral treatment during pregnancy (Treated group). The frequency of NK cells in peripheral blood were detected by flow cytometry.

Result: The frequency of NK cells in healthy women [15.30 (12.80, 18.40)] was higher than that in women with HBV infection, but there was no significant statistical difference (=0.436). The frequency of NK cells in CHB group [10.60 (6.00, 18.30)] was higher than those in pregnant CHB women [Untreated: 6.90 (4.89, 10.04), =0.001; Treated: 9.42 (6.55, 14.10), =0.047]. The frequency of NK cells in treated group was significantly higher than that in untreated group ( = 0.019). The frequencies of NK cells, CD56 NK cells and NKp46 NK cells at 12 and 24 weeks postpartum in the untreated group were increased significantly than those before delivery. In treated group, the frequencies of NK cells, CD56 NK cells, NKp46 NK cells and NKp46 NK cells were significantly increased at 6 and 12 weeks than those before delivery. The frequencies of NK cells and CD56 NK cells postpartum were increased significantly in treated group than those in untreated group. The frequencies of CD56 NK cells decreased significantly after delivery in treated than those in untreated patients. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) significantly increased after delivery than those before delivery. The results showed that the postpartum ALT level was weak positive correlated with NKp46 frequency (=0.199) and was weak negative correlated with NKp46 frequency (= -0.199).

Conclusion: Antiviral treatment during pregnancy could significantly increase the frequency of NK cells postpartum. Postpartum hepatitis may be related to the immune injury caused by change of NK cell frequency and HBV infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2022.893628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168030PMC
June 2022

Excessive branched-chain amino acid accumulation restricts mesenchymal stem cell-based therapy efficacy in myocardial infarction.

Signal Transduct Target Ther 2022 Jun 3;7(1):171. Epub 2022 Jun 3.

Department of Cardiology, Xijing Hospital, the Fourth Military Medical University, 710032, Xi'an, China.

Mesenchymal stem cells (MSCs) delivered into the post-ischemic heart milieu have a low survival and retention rate, thus restricting the cardioreparative efficacy of MSC-based therapy. Chronic ischemia results in metabolic reprogramming in the heart, but little is known about how these metabolic changes influence implanted MSCs. Here, we found that excessive branched-chain amino acid (BCAA) accumulation, a metabolic signature seen in the post-ischemic heart, was disadvantageous to the retention and cardioprotection of intramyocardially injected MSCs. Discovery-driven experiments revealed that BCAA at pathological levels sensitized MSCs to stress-induced cell death and premature senescence via accelerating the loss of histone 3 lysine 9 trimethylation (H3K9me3). A novel mTORC1/DUX4/KDM4E axis was identified as the cause of BCAA-induced H3K9me3 loss and adverse phenotype acquisition. Enhancing BCAA catabolic capability in MSCs via genetic/pharmacological approaches greatly improved their adaptation to the high BCAA milieu and strengthened their cardioprotective efficacy. We conclude that aberrant BCAA accumulation is detrimental to implanted MSCs via a previously unknown metabolite-signaling-epigenetic mechanism, emphasizing that the metabolic changes of the post-ischemic heart crucially influence the fate of implanted MSCs and their therapeutic benefits.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41392-022-00971-7DOI Listing
June 2022

Risk factors of disease flares in a Chinese lupus cohort with low-grade disease activity.

Lupus Sci Med 2022 05;9(1)

Department of Rheumatology, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China

Objective: Recurrent disease flare is one of the key problems in lupus patients. A Chinese Flare-Prevention Lupus Initiative Cohort (FLIC) was established. Risk factors of disease flare were evaluated accordingly.

Methods: Patients with low-grade disease activity (the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) =≤6, daily prednisone ≤20 mg, no British Isles Lupus Assessment Group A or no more than one B organ domain score) from January 2014 to August 2020 were included in the FLIC. Disease flares were defined by the modified SELENA--SLEDAI Flare Index. Low disease activity status (LDAS) and remission were also assessed. The cumulative flare rate was estimated by an event per 100 person-years analysis. Cox proportional hazards models were performed to identify risk factors of subsequent disease flares after adjusting clinical confounders. Survival was assessed with the Kaplan-Meier method.

Results: 448 eligible patients with low-grade disease activity were included in FLIC. During a mean follow-up of 30.4 months, 170 patients flared. The cumulative lupus flare rate was 22.2 events per 100 patient-years. Compared with patients without flare, those with lupus flares were taking more prednisone, had higher disease activity index and with less patients attained LDAS/remission at baseline. They also had higher rates of antiphospholipid antibodies (aPLs) and antiribosomal P antibody. Cox regression analysis confirmed that attainment of either LDAS or remission at baseline were independent protective factors against subsequent disease flare (LDAS but not in remission: HR 0.58, 95% CI 0.38~0.88; remission: HR 0.46, 95% CI 0.30~0.69), while aPL was a risk factor of lupus flares (HR 1.95, 95% CI 1.36~2.78). Kaplan-Meier curves indicated that attaining LDAS or remission and absence of aPL at baseline had the least flare risk.

Conclusions: In our real-world cohort study, not attaining LDAS or remission at baseline and aPL positivity was associated with higher risk of disease flares in patients with low-grade SLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/lupus-2022-000657DOI Listing
May 2022

Dynamic Changes of Cytokine Profiles and Virological Markers Associated With HBsAg Loss During Peginterferon Alpha-2a Treatment in HBeAg-Positive Chronic Hepatitis B Patients.

Front Immunol 2022 4;13:892031. Epub 2022 May 4.

Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Objective: To explore dynamic changes of cytokines and virological markers associated with hepatitis B surface antigen (HBsAg) loss during peginterferon alpha-2a (PEG-IFN α-2a) treatment in hepatitis B e antigen (HBeAg) positive chronic hepatitis B (CHB) patients.

Methods: It was a single-center prospective cohort study. HBeAg-positive CHB patients were prospectively and consecutively enrolled. Cytokines were detected at baseline, week 12 and 24 of PEG-IFN treatment. HBsAg disappearance rate was the primary evaluation index at 48 weeks of PEG-IFN treatment.

Results: Among 100 patients who completed the 48-week PEG-IFN α-2a treatment, 38 patients achieved serum HBeAg disappearance, 25 patients achieved HBeAg seroconversion, 9 patients achieved functional cure, 37 patients had HBsAg decline of ≥1 log IU/ml, and 8 patients produced hepatitis B surface antibody (HBsAb). Albumin (ALB), fms-like tyrosine kinase 3 ligand (FLT3-L) and interferon-alpha2 (IFN-α2) in the clinical cure group were significantly lower than those in the non-clinical-cure group at baseline. After 12 weeks of treatment, HBsAg in the clinical cure group was significantly lower than that in the non-clinical-cure group (median 1.14 vs. 3.45 log10IU/ml, Z=-4.355, < 0.001). The decrease of HBsAg and hepatitis B virus desoxyribose nucleic acid (HBV DNA) in the clinical cure group was significantly higher than that in non-clinical-cure group (median: HBsAg 1.96 vs. 0.33 log10IU/ml, Z=-4.703, < 0.001; HBV DNA 4.49 vs.3.13 logIU/ml, Z=-3.053, =0.002). The increase of IFN-α2 in the cure group was significantly higher than that in the non-clinical-cure group (497.89 vs. 344.74, Z=-2.126, =0.034). After 24 weeks of treatment, HBsAg, HBeAg, Flt3-L, and IL-10 in the clinical cure group were significantly lower than those in the non-clinical-cure group (median: HBsAg 0.70 vs. 3.15 logIU/ml, Z=-4.535, P< 0.001; HBeAg 1.48 vs. 13.72 S/CO, Z = 2.512, = 0.012; Flt3-l 0.00 vs 2.24 pg/ml, Z = 3.137, =0.002; IL-10 0.70 vs. 2.71 pg/ml, Z=-4.067, < 0.001). HBsAg decreased significantly in the clinical cure group compared with non-clinical-cure group (median 3.27 vs. 0.45, Z=-4.463, < 0.001).

Conclusion: Dynamic changes of cytokines and virology markers during early PEG IFN α-2a treatment were associated with HBsAg loss in HBeAg-positive CHB patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2022.892031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114800PMC
May 2022

Phylogeography of in relation to Quaternary climatic aridification and oscillations in northwestern China.

PeerJ 2022 29;10:e13345. Epub 2022 Apr 29.

General grassland station of Xinjiang, Urumqi, Xingjiang, China.

Quaternary period geological events and climatic oscillations significantly affect the geographic structure and genetic diversity of species distribution in arid northwestern China. is a relict and endangered shrub that occurs primarily in arid areas of northwestern China. Based on variation patterns present at three cpDNA regions (K-I, L-F and V) and in one nDNA sequence (ITS1-ITS4) in 174 individuals representing 15 populations, the spatial genetic structure and demographic history of was examined across its entire geographic range. The 17 different haplotypes and 10 ribotypes showed two lineages, distributed across the Western (Mazong Mountains, Hexi Corridor, and Alxa Left Banner) and Eastern regions (Urad Houqi, Yinshan Mountains, Urad Zhongqi, and Daqing Mountains) according to the median-joining network and the BI (Bayesian inference) and ML (Maximum likelihood) trees. AMOVA analysis demonstrated that over 65% of the observed genetic variation was related to this lineage split. The expansions of the Ulanbuhe and Tengger deserts and the eastward extension of the Yinshan Mountains since the Quaternary period likely interrupted gene flow and triggered the observed divergence in the two allopatric regions; arid landscape fragmentation accompanied by local environmental heterogeneity further increased local adaptive differentiation between the Western and Eastern groups. Based on the evidence from phylogeographical patterns and the distribution of genetic variation, distributed in the eastern and western regions are speculated to have experienced eastward migration along the southern slopes of the Lang Mountains and westward migration along the margins of the Ulanbuhe and Tengger deserts to the Hexi Corridor, respectively. For setting a conservation management plan, it is recommended that the south slopes of the Lang Mountains and northern Helan Mountains be identified as the two primary conservation areas, as they have high genetic variation and habitats that are more suitable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.13345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9059755PMC
April 2022

Ferroptosis-based molecular prognostic model for adrenocortical carcinoma based on least absolute shrinkage and selection operator regression.

J Clin Lab Anal 2022 Jun 2;36(6):e24465. Epub 2022 May 2.

Department of Endocrinology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: This study aimed to find ferroptosis-related genes linked to clinical outcomes of adrenocortical carcinoma (ACC) and assess the prognostic value of the model.

Methods: We downloaded the mRNA sequencing data and patient clinical data of 78 ACC patients from the TCGA data portal. Candidate ferroptosis-related genes were screened by univariate regression analysis, machine-learning least absolute shrinkage, and selection operator (LASSO). A ferroptosis-related gene-based prognostic model was constructed. The effectiveness of the prediction model was accessed by KM and ROC analysis. External validation was done using the GSE19750 cohort. A nomogram was generated. The prognostic accuracy was measured and compared with conventional staging systems (TNM stage). Functional analysis was conducted to identify biological characterization of survival-associated ferroptosis-related genes.

Results: Seventy genes were identified as survival-associated ferroptosis-related genes. The prognostic model was constructed with 17 ferroptosis-related genes including STMN1, RRM2, HELLS, FANCD2, AURKA, GABARAPL2, SLC7A11, KRAS, ACSL4, MAPK3, HMGB1, CXCL2, ATG7, DDIT4, NOX1, PLIN4, and STEAP3. A RiskScore was calculated for each patient. KM curve indicated good prognostic performance. The AUC of the ROC curve for predicting 1-, 3-, and 5- year(s) survival time was 0.975, 0.913, and 0.915 respectively. The nomogram prognostic evaluation model showed better predictive ability than conventional staging systems.

Conclusion: We constructed a prognosis model of ACC based on ferroptosis-related genes with better predictive value than the conventional staging system. These efforts provided candidate targets for revealing the molecular basis of ACC, as well as novel targets for drug development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcla.24465DOI Listing
June 2022

Ultra-specific genotyping of single nucleotide variants by ligase-based loop-mediated isothermal amplification coupled with a modified ligation probe.

RSC Adv 2021 May 10;11(28):17058-17063. Epub 2021 May 10.

Department of Gynecology, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 Henan Province P. R. China

Specific and accurate detection of single nucleotide variants (SNVs) plays significant roles in pathogenic gene research and clinical applications. However, the sensitive but ultra-specific detection of rare variants in biological samples still remains challenging. Herein, we report a novel, robust and practical SNV assay by integrating the outstanding features of high selectivity of an artificial mismatched probe, and the powerful loop-mediated isothermal amplification. In this strategy, we rationally introduce artificial mismatched bases into the 3'-terminal regions of the probe located in the ligation region to reduce the risk of nonspecific ligation, which can dramatically improve the specificity for the SNV assay. The proposed method can discern as little as 0.01% mutant DNA in the high background of wild-type DNA with high sensitivity (10 aM). In virtue of its outstanding performance, the artificial mismatched probe may also be employed and expanded in various DNA and RNA genetic analyses with ligase-assisted approaches, showing great potential in biomedical research, clinical diagnostics, and bioanalysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1ra00851jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032167PMC
May 2021

Small Extracellular Vesicles From Brown Adipose Tissue Mediate Exercise Cardioprotection.

Circ Res 2022 May 7;130(10):1490-1506. Epub 2022 Apr 7.

Department of Cardiology (H.Z., X.C., G.H., C.L., L.G., L.Z., F.S., Y.X., W.Y., Z.C., Y.G., X.G., C.H., M.F., S.W., F.Z., L.T.).

Rationale: Long-term exercise provides reliable cardioprotection via mechanisms still incompletely understood. Although traditionally considered a thermogenic tissue, brown adipose tissue (BAT) communicates with remote organs (eg, the heart) through its endocrine function. BAT expands in response to exercise, but its involvement in exercise cardioprotection remains undefined.

Objective: This study investigated whether small extracellular vesicles (sEVs) secreted by BAT and their contained microRNAs (miRNAs) regulate cardiomyocyte survival and participate in exercise cardioprotection in the context of myocardial ischemia/reperfusion (MI/R) injury.

Methods And Results: Four weeks of exercise resulted in a significant BAT expansion in mice. Surgical BAT ablation before MI/R weakened the salutary effects of exercise. Adeno-associated virus 9 vectors carrying short hairpin RNA targeting (a GTPase required for sEV secretion) or control viruses were injected in situ into the interscapular BAT. Exercise-mediated protection against MI/R injury was greatly attenuated in mice whose BAT sEV secretion was suppressed by silencing. Intramyocardial injection of the BAT sEVs ameliorated MI/R injury, revealing the cardioprotective potential of BAT sEVs. Discovery-driven experiments identified miR-125b-5p, miR-128-3p, and miR-30d-5p (referred to as the BAT miRNAs) as essential BAT sEV components for mediating cardioprotection. BAT-specific inhibition of the BAT miRNAs prevented their upregulation in plasma sEVs and hearts of exercised mice and attenuated exercise cardioprotection. Mechanistically, the BAT miRNAs cooperatively suppressed the proapoptotic MAPK (mitogen-associated protein kinase) pathway by targeting a series of molecules (eg, , , and ) in the signaling cascade. Delivery of BAT sEVs into hearts or cardiomyocytes suppressed MI/R-related MAPK pathway activation, an effect that disappeared with the combined use of the BAT miRNA inhibitors.

Conclusions: The sEVs secreted by BAT participate in exercise cardioprotection via delivering the cardioprotective miRNAs into the heart. These results provide novel insights into the mechanisms underlying the BAT-cardiomyocyte interaction and highlight BAT sEVs and their contained miRNAs as alternative candidates for exercise cardioprotection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCRESAHA.121.320458DOI Listing
May 2022

Consolidation treatment needed for sustained HBsAg-negative response induced by interferon-alpha in HBeAg positive chronic hepatitis B patients.

Virol Sin 2022 Jun 4;37(3):390-397. Epub 2022 Mar 4.

Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China; Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, 100015, China. Electronic address:

Hepatitis B surface antigen (HBsAg) clearance is considered as functional cure in patients with chronic hepatitis B (CHB). This study aimed to assess the durability of HBsAg clearance achieved by interferon-based therapies in patients with CHB who were originally positive for hepatitis B envelope antigen (HBeAg). In this prospective study, HBeAg-positive CHB patients with confirmed HBsAg loss under interferon-based therapies were enrolled within 12 weeks from end of treatment and followed up for 48 weeks. Virological markers, biochemical indicators, and liver imaging examinations were observed every 3-6 months. Sustained functional cure was analysed as primary outcome. Factor associated with sustained HBsAg loss or reversion was also investigated. The rate of HBsAg loss sustainability was 91.8% (212/231). Patients receiving consolidation treatment for 12-24 weeks or ≥ 24 weeks had higher rates of sustained HBsAg negativity than those receiving consolidation treatment for < 12 weeks (98.3% and 91.2% vs. 86.7%, P ​= ​0.068), and the former groups had significantly higher anti-HBs levels than the later (P ​< ​0.05). The cumulative incidence of HBsAg reversion and HBV DNA reversion was 8.2% and 3.9%, respectively. Consolidation treatment of ≥ 12 weeks [odd ratio (OR) 3.318, 95% confidence interval (CI) 1.077-10.224, P ​= ​0.037) was a predictor of sustained functional cure, and HBeAg-positivity at cessation of treatment (OR 12.271, 95% CI 1.076-139.919, P ​= ​0.043) was a predictor of HBsAg reversion. Interferon-alpha induced functional cure was durable and a consolidation treatment of ≥ 12-24 weeks was needed after HBsAg loss in HBeAg-positive CHB patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.virs.2022.03.001DOI Listing
June 2022

Successful treatment of sirolimus in a Chinese patient with refractory LN and APS: a case report.

Ther Adv Musculoskelet Dis 2022 28;14:1759720X221079253. Epub 2022 Feb 28.

Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 2000 Jiangyue Road, Shanghai, 201112, China.

It has been reported that the mammalian target of rapamycin (mTOR) pathway is involved in the pathogenesis of systemic lupus erythematosus (SLE), and increasing evidence has shown the effect of mTOR-targeted therapies with sirolimus in SLE. The objective of this study was to report the successful treatment of sirolimus in a Chinese patient with refractory lupus nephritis (LN) and anti-phospholipid antibody syndrome (APS). A 44-year-old female with a previous diagnosis of autoimmune hemolytic anemia (AIHA) and APS secondary to SLE presented with lupus nephritis refractory to cyclophosphamide and mycophenolate. Renal biopsy met the criteria of WHO class III LN complicated by acute tubular injury and immunofluorescence confirmed the activation of the mTOR pathway. Treatment with the mTOR inhibitor sirolimus was initiated in this patient. Complete remission (CR) was achieved after 6 months, and flare-free remission was maintained for the next 3.5 years. The literature on the efficacy of sirolimus in patients with LN was reviewed. Although the available evidence is limited to retrospective studies with small sample sizes, sirolimus appeared to be efficacious in some patients with refractory LN. Well-designed clinical trials are warranted, and pathology-guided precision medicine might assist in guiding physicians' treatment decisions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1759720X221079253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891858PMC
February 2022

The adaptive evolution of Euryale ferox to the aquatic environment through paleo-hexaploidization.

Plant J 2022 05 27;110(3):627-645. Epub 2022 Mar 27.

School of Horticulture and Plant Protection, Yangzhou University, Yangzhou, 225000, China.

Occupation of living space is one of the main driving forces of adaptive evolution, especially for aquatic plants whose leaves float on the water surface and thus have limited living space. Euryale ferox, from the angiosperm basal family Nymphaeaceae, develops large, rapidly expanding leaves to compete for space on the water surface. Microscopic observation found that the cell proliferation of leaves is almost completed underwater, while the cell expansion occurs rapidly after they grow above water. To explore the mechanism underlying the specific development of leaves, we performed sequences assembly and analyzed the genome and transcriptome dynamics of E. ferox. Through reconstruction of the three sub-genomes generated from the paleo-hexaploidization event in E. ferox, we revealed that one sub-genome was phylogenetically closer to Victoria cruziana, which also exhibits gigantic floating leaves. Further analysis revealed that while all three sub-genomes promoted the evolution of the specific leaf development in E. ferox, the genes from the sub-genome closer to V. cruziana contributed more to this adaptive evolution. Moreover, we found that genes involved in cell proliferation and expansion, photosynthesis, and energy transportation were over-retained and showed strong expression association with the leaf development stages, such as the expression divergence of SWEET orthologs as energy uploaders and unloaders in the sink and source leaf organs of E. ferox. These findings provide novel insights into the genome evolution through polyploidization, as well as the adaptive evolution regarding the leaf development accomplished through biased gene retention and expression sub-functionalization of multi-copy genes in E. ferox.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tpj.15717DOI Listing
May 2022

Benefits of intraoral stents for sparing normal tissue in radiotherapy of nasopharyngeal carcinoma: a radiobiological model-based quantitative analysis.

Transl Cancer Res 2021 Oct;10(10):4281-4289

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Background: To determine the value of individualized intraoral stent for normal tissue sparing in radiotherapy of nasopharyngeal carcinoma (NPC) using quantitative analysis of radiobiological model.

Methods: Sixteen patients with NPC who used intraoral stent and 17 patients without intraoral stent were enrolled in this study. All patients underwent Helical Tomotherapy (HT) in our center. Based on the patient's dose volume histogram (DVH), the modified Webb-Nahum model was used to predict tumor control probability (TCP), and the parallel architecture model and Lyman-Kutcher-Burman (LKB) model were used to estimate the normal tissue complications probability (NTCP). The differences of TCP, NTCP and dosimetric parameters between the two groups were compared and analyzed.

Results: The mean dose metrics of oral cavity, mandible, left and right parotid gland in patients with intraoral stent was significantly decreased by 11.6%, 12.2%, 15.4%, and 8.7% on average, respectively (P<0.05), while the conformity index (CI, P=0.056) and homogeneity index (HI, P=0.676) of the tumor target showed no statistically different. Quantitative assessment of radiobiological model revealed that the NTCP of oral cavity and parotid glands were both significantly lower in patients with intraoral stent than those without intraoral stent (P<0.001), without compromising TCP of the tumor target (P=0.056). For example, patients using intraoral stent significantly reduced oral mucositis and xerostomia complication probability by 2.52% and 10.11% on average compared to unused ones, respectively.

Conclusions: The custom-made intraoral stents showed promising value at sparing normal tissue during radiotherapy for NPC without affecting target dose coverage or tumor control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tcr-21-1324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8797929PMC
October 2021

Low-dose belimumab for patients with systemic lupus erythematosus at low disease activity: protocol for a multicentre, randomised, double-blind, placebo-controlled clinical trial.

Lupus Sci Med 2022 02;9(1)

Department of Rheumatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

Introduction: SLE is a chronic inflammatory systemic autoimmune disease with relapsing-remitting pattern. B-lymphocyte stimulator was involved in the pathogenesis of SLE. The humanised monoclonal antibody belimumab with 10 mg/kg was effective for active patients. However, the efficacy of low-dose belimumab for prevention of disease flares in patients with SLE with low disease activity is to be explored.

Methods And Analysis: This is a multicentre, randomised, double-blind, placebo-controlled clinical trial. Patients who have Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) scores no higher than 6; with no A score or no more than one B score on the British Isles Lupus Assessment Group (BILAG) scale; and who are treated with prednisone (≤20 mg per day) at screening will be enrolled. 334 adults will be randomly assigned in a 1:1 ratio to receive intravenous 120 mg belimumab or placebo (saline) arm on weeks 0, 2, and 4, and then every 4 weeks until 48 weeks, with standard of care. The primary outcome measure is a composite index of severe or mild-to-moderate disease flares (SELENA-SLEDAI Flare Index) within 52 weeks. Secondary outcomes include the percentage of severe flare, the percentage of mild-to-moderate flare, time to first disease flare, changes in prednisone dose, SELENA-SLEDAI, as well as BILAG score, the percentage of patients achieving prednisone free and safety analysis.

Ethics And Dissemination: The protocol has been approved by the Ethics Committee of the Renji Hospital, Huashan Hospital and the Sixth People's Hospital. The trial has been registered and the detailed information is available at https://clinicaltrialsgov/ct2/show/NCT04515719. The results of this clinical trial will be submitted for publication in peer-reviewed journals and key findings will also be presented at national and international conferences.

Trial Registration Number: NCT04515719.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/lupus-2021-000638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8808446PMC
February 2022

Advances in Metagenomics and Its Application in Environmental Microorganisms.

Front Microbiol 2021 17;12:766364. Epub 2021 Dec 17.

Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Metagenomics is a new approach to study microorganisms obtained from a specific environment by functional gene screening or sequencing analysis. Metagenomics studies focus on microbial diversity, community constitute, genetic and evolutionary relationships, functional activities, and interactions and relationships with the environment. Sequencing technologies have evolved from shotgun sequencing to high-throughput, next-generation sequencing (NGS), and third-generation sequencing (TGS). NGS and TGS have shown the advantage of rapid detection of pathogenic microorganisms. With the help of new algorithms, we can better perform the taxonomic profiling and gene prediction of microbial species. Functional metagenomics is helpful to screen new bioactive substances and new functional genes from microorganisms and microbial metabolites. In this article, basic steps, classification, and applications of metagenomics are reviewed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.766364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8719654PMC
December 2021

Attaining treat-to-target endpoints with metformin in lupus patients: a pooled analysis.

Clin Exp Rheumatol 2021 12 7. Epub 2021 Dec 7.

Department of Rheumatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Objectives: Low disease activity status and remission are crucial treat-to-target (T2T) endpoints in systemic lupus erythematosus (SLE). To evaluate the efficacy of metformin add-on in attaining T2T among Chinese patients with mild-to-moderate lupus, a post-hoc analysis combining our previous two randomised trials was carried out.

Methods: Data from the open-labeled proof-of-concept trial (ChiCTR-TRC-12002419) and placebo-controlled trial (NCT02741960) were integrated together. Disease flares were compared between patients attaining T2T or not at baseline. The efficacy of metformin versus placebo/nil add-on to standard therapy in SLE patients who did not meet the T2T criteria at baseline was evaluated in terms of attaining T2T at 12-month follow-up.

Results: Of 253 SLE patients, 43.8% (n=89) attained T2T at baseline. During the 12 months, 15 patients flared in the T2T group, which was significantly lower than that in the non-T2T group (16.9% vs. 36.0%, p=0.001). For 164 patients who did not meet the T2T criteria at entry, 59.0% and 43.6% of the 78 patients taking metformin in this population attained the lupus low disease activity status (LLDAS) and remission endpoints at last visit, respectively, as compared to 37.2% and 24.4% of the 86 patients in the placebo/nil group (LLDAS p=0.008; remission p=0.013). Over time, metformin helped patients achieving T2T earlier and maintain longer T2T duration over placebo/nil (LLDAS duration: 44.9% vs. 26.4%, p=0.002; remission duration:19.1% vs. 10.7%, p=0.014).

Conclusions: This post-hoc analysis suggested that metformin might be an adjuvant therapy in achieving treat-to-target in SLE patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2021

Application of Lab-on-Chip for Detection of Microbial Nucleic Acid in Food and Environment.

Front Microbiol 2021 4;12:765375. Epub 2021 Nov 4.

Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Various diseases caused by food-borne or environmental pathogenic microorganisms have been a persistent threat to public health and global economies. It is necessary to regularly detect microorganisms in food and environment to prevent infection of pathogenic microorganisms. However, most traditional detection methods are expensive, time-consuming, and unfeasible in practice in the absence of sophisticated instruments and trained operators. Point-of-care testing (POCT) can be used to detect microorganisms rapidly on site and greatly improve the efficiency of microbial detection. Lab-on-chip (LOC) is an emerging POCT technology with great potential by integrating most of the experimental steps carried out in the laboratory into a single monolithic device. This review will primarily focus on principles and techniques of LOC for detection of microbial nucleic acid in food and environment, including sample preparation, nucleic acid amplification and sample detection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2021.765375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600318PMC
November 2021

One-year renal outcome in lupus nephritis patients with acute kidney injury: a nomogram model.

Rheumatology (Oxford) 2021 Nov 2. Epub 2021 Nov 2.

Department of Rheumatology, Ren Ji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Objective: To develop a short-term renal outcome prediction model for acute kidney injury (AKI) in patients with lupus nephritis.

Methods: Two lupus AKI cohorts from 2 independent centers during 2013-2019 were included, i.e., a derivation cohort from a rheumatology center and a validation cohort from a nephrology center. Clinical characteristics and renal histologic features were obtained. The outcome measurement was the recovery of kidney function within 12-month. Lasso regression was used for feature selection. Prediction models with or without pathology were built and nomogram was plotted. Model evaluation including calibration curve and decision curve analysis was performed.

Results: 130 patients and 96 patients were included in the derivation and validation cohorts, of which 82 and 73 patients received renal biopsy, respectively. The prognostic nomogram model without pathology included determinants of SLE duration, days from AKI onset to treatment and baseline creatinine level (C-index 0.85 (95%CI 0.78∼0.91) and 0.79 (95%CI 0.70∼0.88) for the 2 cohorts). Combination of histologic interstitial tubular fibrosis in the nomogram gave an incremental predictive performance (C-index 0.93 vs 0.85, p = 0.039) in the derivation cohort, but failed to improve the performance in the validation cohort (C-index 0.81 vs 0.79, p = 0.78). Decision curve analysis suggested clinical benefit of the prediction models.

Conclusion: The predictive nomogram models might facilitate more accurate management for lupus patients with AKI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keab818DOI Listing
November 2021

An ultrasound-driven immune-boosting molecular machine for systemic tumor suppression.

Sci Adv 2021 Oct 20;7(43):eabj4796. Epub 2021 Oct 20.

State Key Laboratory of Fine Chemicals, Department of Pharmacy, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China.

Exploring facile and effective therapeutic modalities for synergistically controlling primary tumor and metastasis remains a pressing clinical need. Sonodynamic therapy (SDT) offers the possibility of noninvasively eradicating local solid tumors, but lacks antimetastatic activity because of its limited ability in generating systemic antitumor effect. Here, we exploited a previously unidentified ultrasound-driven “molecular machine,” DYSP-C34 (C34 for short), with multiple attractive features, emerging from preferential tumor accumulation, potent ultrasound-triggered cytotoxicity, and intrinsic immune-boosting capacity. Driven by the ultrasound, C34 functioned not only as a tumor cell killing reagent but also as an immune booster that could potentiate robust adaptive antitumor immunity by directly stimulating dendritic cells, resulting in the eradication of the primary solid tumor along with the inhibition of metastasis. This molecular machine, C34, rendered great promise to achieve systemic treatment against cancer via unimolecule-mediated SDT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abj4796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8528430PMC
October 2021

Description and Analysis of a Novel Subtype of the Anti-Synthetase Syndrome Characterized by Frequent Attacks of Fever and Systemic Inflammation in a Single-Center Cohort Study.

Front Immunol 2021 23;12:729602. Epub 2021 Sep 23.

Department of Rheumatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Objectives: The aim of this study was to investigate anti-synthetase syndrome (ASyS) patients who presented with recurrent episodes of fever and systemic inflammation.

Methods: A retrospective cohort of Chinese ASyS patients (n=126) in our center (between January 2013 and January 2020) was included. Patients presenting with concomitant autoimmune rheumatic diseases or malignancies were subsequently excluded. The number of non-infectious fever attacks and attack frequency were recorded and calculated. Patients with two or more attacks and within the upper three quartiles of attack frequency were defined as high-inflammation group. Univariate and multivariate analyses were carried out to characterize the high-inflammation subtype.

Results: Out of 113 eligible patients with an average of 5 years follow up, 25 patients were defined as the high-inflammation group (16 for anti-Jo1, 9 for anti-PL7), with an average of 1.12 attack/patient-year. Compared to low-inflammation group (0-1 attack only and a frequency lower than 0.5 attack/patient-year), the high-inflammation group had higher occurrence of fever and rapid progressive interstitial lung disease (RPILD) as the first presentation (84% 21% and 40% 9%, respectively, both p<0.01). Anti-PL-7 was related to the more inflammatory phenotype (p=0.014). Cumulative disease-modifying agent exposures (>=3) were much higher in the high-inflammation group (60% 26%), while biological agents, i.e., rituximab and tocilizumab, showed better "drug survival" for Jo-1+ and PL-7+ ASyS patients with high inflammation, respectively, in our cohort.

Conclusions: ASyS with recurrent systemic inflammatory episodes reflects a subtype of more aggressive and refractory disease in the spectrum of ASyS. Increased awareness of this subtype might lead to more appropriate management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.729602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495196PMC
December 2021

The risk factors of heart failure in elderly patients with hip fracture: what should we care.

BMC Musculoskelet Disord 2021 Sep 28;22(1):832. Epub 2021 Sep 28.

Department of Rehabilitation Medicine, Tongji Medical College, The Central Hospital of Wuhan, Huazhong University of Science and Technology, No.26 Shengli Street, Jiang'an District, Wuhan City, Hubei Province, China.

Background: Heart failure is a common adverse postoperative complication in elderly patients. It is necessary to explore the risk factors of heart after the operation of elderly patients with hip fracture during hospitalization.

Methods: Patients with hip fractures admitted to our hospital from January 1, 2019 to December 31 2020 were included, all the patients received internal fixation surgery. The characteristics of patients with and without postoperative heart failure were compared. Multivariate logistic regression analyses were applied to analyze the risk factors of heart failure in elderly patients with hip fracture.

Results: A total of 283 patients with hip fractures were included, the incidence of heart failure was 12.37 %. There were significant differences in the age, hypertension, anemia hypoalbuminemia and duration of surgery between heart failure and no heart failure group(all p < 0.05). There were no significant differences in the gender, BMI, diabetes mellitus, hyperlipidemia, history of heart failure, cognitive dysfunction, type of fracture, preoperative oxygen saturation, white blood cell count, platelet count, red blood cell count, creatinine, alanine aminotransferase, aspartate aminotransferase and estimated blood loss during surgery between heart failure and no heart failure group(all p > 0.05). Logistic regression analyses indicated that age ≥ 70y(OR2.446, 95% CI1.044 ~ 4.149), hypertension(OR2.152, 95% CI1.125 ~ 4.023), anemia(OR3.094, 95% CI1.294 ~ 5.907), hypoalbuminemia(OR2.377, 95% CI1.205 ~ 4.537), duration of surgery ≥ 120 min(OR1.683, 95% CI1.094 ~ 2.782) were the risk factors of heart failure in elderly patients with hip fracture(all p < 0.05).

Conclusions: The incidence of postoperative heart failure in elderly patients with hip fracture is relatively high, which is the result of a combination of high-risk factors. Peri-period risk assessment and prevention of related risks are the keys to a good prognosis for patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12891-021-04686-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8479890PMC
September 2021

Effects of surface treatments on the bonding properties of polyetherketoneketone to dentin: An in vitro study.

J Prosthet Dent 2021 Nov 17;126(5):709.e1-709.e10. Epub 2021 Sep 17.

Associate Professor, Department of Prosthodontics, Stomatological Digital Engineering Center, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, PR China. Electronic address:

Statement Of Problem: Polyetherketoneketone (PEKK) has been recently introduced as a dental material for fixed dental prostheses. However, how surface treatments affect the bonding of PEKK to dentin is unclear.

Purpose: The purpose of this in vitro study was to evaluate the effects of airborne-particle abrasion and acid etching on the bonding of PEKK to dentin.

Material And Methods: Eighty-four PEKK specimens were fabricated, polished, and divided into 6 groups (n=14): no treatment (group NT), airborne-particle abrasion with 110-μm alumina particles (group Al), 98% sulfuric acid etching for 5 seconds (group SA5), 98% sulfuric acid etching for 30 seconds (group SA30), 98% sulfuric acid etching for 60 seconds (group SA60), and airborne-particle abrasion plus 98% sulfuric acid for 5 seconds (group AlSA5). Sixty PEKK specimens (n=10) were fabricated for the shear bond test. Another 24 PEKK specimens (n=4) were fabricated for surface element analysis and morphological observations. For each group, 2 specimens after surface treatments were randomly selected to examine scanning electron microscope (SEM) observations and surface element analysis. Another 2 specimens after bonding were randomly selected to examine cross-sectional observations. Airborne-particle abrasion with 110-μm alumina particles was performed to cobalt-chromium (Co-Cr) specimens (group Co-Cr, n=10). A light-polymerizing polymethylmethacrylate and composite resin primer (visio.link) was applied to the treated PEKK specimens and bonded with a resin cement (RelyX Ultimate) to dentin. The Co-Cr specimens were bonded with the resin cement to dentin. The shear bond strengths of all groups were tested by using a universal testing machine, and fracture analysis was performed. A statistical analysis was performed by using 1-way ANOVA, followed by the Student-Newman-Keuls-q post hoc test (α=.05).

Results: The shear bond strengths of groups SA5 and AlSA5 were higher than those of groups NT, Al, SA30, SA60, and Co-Cr (P<.05). Group SA5 achieved the highest shear bond strength (16.84 ±1.84 MPa). The SEM observations showed that after surface treatments, groups SA5 and AlSA5 had a uniform sponge shape with small pores, while groups SA30 and SA60 had a collapsed shape with large pits and pores. The sulfur element content and HSO-etched thicknesses of groups SA30 and SA60 were higher than those of groups SA5 and AlSA5. The cross-sectional SEM observations of groups SA30 and SA60 after bonding revealed that HSO-etched pores were deeper and not filled with the bonding material.

Conclusions: Compared with airborne-particle abrasion, the 98% sulfuric acid etching significantly improved the shear bond strength of PEKK to dentin. The surface treatment of 98% sulfuric acid etching for 5 seconds led to the high bond strength of PEKK to dentin, which meets the requirements for clinical use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prosdent.2021.08.012DOI Listing
November 2021

Diurnal regulation of oxidative phosphorylation restricts hepatocyte proliferation and inflammation.

Cell Rep 2021 09;36(10):109659

School of Life Sciences, Tsinghua University, Beijing, China 100084; Department of Basic Research, Guangzhou Laboratory, Guangdong, China 510005. Electronic address:

The principles guiding the diurnal organization of biological pathways remain to be fully elucidated. Here, we perturb the hepatic transcriptome through nutrient regulators (high-fat diet and mTOR signaling components) to identify enduring properties of pathway organization. Temporal separation and counter-regulation between pathways of energy metabolism and inflammation/proliferation emerge as persistent transcriptome features across animal models, and network analysis identifies the G0s2 and Rgs16 genes as potential mediators at the metabolism-inflammation interface. Mechanistically, G0s2 and Rgs16 are sequentially induced during the light phase, promoting amino acid oxidation and suppressing overall mitochondrial respiration. In their absence, sphingolipids and diacylglycerides accumulate, accompanied by hepatic inflammation and hepatocyte proliferation. Notably, the expression of G0s2 and Rgs16 is further induced in obese mouse livers, and silencing of their expression accentuates hepatic fibrosis. Therefore, diurnal regulation of energy metabolism alleviates inflammatory and proliferative stresses under physiological and pathological conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2021.109659DOI Listing
September 2021

Effects of valsartan combined with α-lipoic acid on renal function in patients with diabetic nephropathy: a systematic review and meta-analysis.

BMC Endocr Disord 2021 Aug 31;21(1):178. Epub 2021 Aug 31.

Department of Pathology, Zhejiang Province People's Hospital, Hangzhou, 310014, China.

Background: Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes, valsartan and α-lipoic acid alone or in combination has been used for the treatment of patients with DN. However, some results in these clinical reports were still controversial. The purpose of this study was to evaluate the efficacy of valsartan combined with α-lipoic acid on renal function in patients with DN.

Methods: We searched the electronic databases including PubMed, Sciencedirect, EMBASE, Cochrane library, Chinese national knowledge infrastructure (CNKI) and Wanfang databases, and the publication deadline was limited to January 2020. Randomized controlled trials (RCTs) evaluating the effects of valsartan combined with α-lipoic acid in DN patients were included. Pooled estimates were conducted using a fixed or random effect model. The outcomes included urinary albumin excretion rate (UAER), and the level of urinary albumin, β-microglobulin (β-MG), hypersensitive C-reactive protein (hs-CRP) and oxidative stress.

Results: 11 studies with 1294 participants were included in this study. The pooled analysis indicated that α-lipoic acid combined with valsartan could remarkably reduce UAER (P < 0.00001, SMD = -1.95, 95%CI = -2.55 to - 1.20; P = 0.03, SMD = -0.85, 95%CI = -1.59 to - 0.1) and the level of urinary albumin (P = 0.001, SMD = -1.48, 95%CI = - 2.38 to - 0.58; P = 0.01, SMD = -1.67, 95%CI = -3.00 to - 0.33), β-MG (P < 0.001,SMD = - 2.59, 95%CI = -3.78 to - 1.40; P = 0.03, SMD = -0.48, 95%CI = -0.93 to - 0.04) when compared with valsartan or lipoic acid monotherapy in patients with DN. However, there was no significant difference in the level of hs-CRP among the three therapies (P = 0.06, SMD = -2.80, 95%CI = -5.67 to 0.07; P = 0.10, SMD = -0.42, 95%CI = - 0.92 to 0.08). In addition, α-lipoic acid combined with valsartan markedly increased the level of SOD (P = 0.03, SMD = 1.24, 95%CI = 0.32 to 1.03; P = 0.0002, SMD = 0.68, 95%CI = 0.32 to 1.03) and T-AOC (P < 0.00001, SMD = 0.89, 95%CI = 0.62 to 1.16; P = 0.02, SMD = 0.58, 95%CI = 0.10 to1.07), and reduced the level of MDA(P = 0.0002, SMD = -1.99, 95%CI = -3.02 to - 0.96; P = 0.0001, SMD = -0.69, 95%CI = -1.04 to - 0.34).

Conclusions: α-lipoic acid combined with valsartan could significantly reduce the level of urinary albumin and oxidative stress, increase antioxidant capacity and alleviate renal function damage in patients with DN, and this will provide a reference for the selection of treatment drugs for DN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12902-021-00844-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406725PMC
August 2021

Long non-coding RNA LINC01207 promotes cell proliferation and migration but suppresses apoptosis and autophagy in oral squamous cell carcinoma by the microRNA-1301-3p/lactate dehydrogenase isoform A axis.

Bioengineered 2021 12;12(1):7780-7793

Department of Prosthodontics, Nanjing Stomatological Hospital Medical School of Nanjing University, Nanjing, China.

Long noncoding RNAs (lncRNAs) have been reported to participate in the progression of various cancers, including oral squamous cell carcinoma (OSCC). This study aims to find out whether lncRNA LINC01207 regulates the progression of OSCC. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was conducted to evaluate gene expression in OSCC cells and tissues. Cell viability, proliferation, migration, apoptosis, and autophagy were detected using Cell Counting Kit-8 (CCK-8), colony formation, Transwell assays, flow cytometry, and western blot analysis. Luciferase reporter and RNA immunoprecipitation (RIP) assays were conducted to assess the interactions among genes. We found that LINC01207 was overexpressed in OSCC cells and tissues. LINC01207 silencing inhibited OSCC cell proliferation and migration but promoted apoptosis and autophagy, and LINC01207 overexpression had an opposite result. LINC01207 interacted with microRNA-1301-3p (miR-1301-3p) while lactate dehydrogenase isoform A (LHDA) was targeted by miR1301-3p. Effects caused by LINC01207 downregulation on OSCC cells were reversed by overexpression of LDHA. Overall, LINC01207 promotes OSCC progression via the miR-1301-3p/LDHA axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21655979.2021.1972784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8806684PMC
December 2021

Riok3 inhibits the antiviral immune response by facilitating TRIM40-mediated RIG-I and MDA5 degradation.

Cell Rep 2021 06;35(12):109272

Cancer Institute, ZJU-UCLA Joint Center for Medical Education and Research, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address:

The type I interferon (IFN) pathway is a key component of innate immune response upon invasion of foreign pathogens. It is also under precise control to prevent excessive upregulation and undesired inflammation cascade. In the present study, we report that Riok3, an atypical kinase, negatively regulates retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) sensing-induced type I IFN signaling. Riok3 deficiency selectively inhibits RNA viral replication in vitro, resulting from an upregulated type I IFN pathway. Mice with myeloid-specific Riok3 knockout also show a more robust induction of type I IFN upon RNA virus infection and are more resistant to RNA virus-induced pathogenesis. Mechanistically, Riok3 recruits and interacts with the E3 ubiquitin ligase TRIM40, leading to the degradation of RIG-I and melanoma differentiation-associated gene-5 (MDA5) via K48- and K27-linked ubiquitination. Collectively, our data reveal the mechanism that Riok3 employs to be a negative regulator of antiviral innate immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2021.109272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363743PMC
June 2021
-->