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Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.
Subject(s)
Humans , 3' Untranslated Regions , Arthritis, Gouty/genetics , Interleukin-1beta/genetics , Interleukin-8 , Luciferases , MicroRNAs/genetics , Tumor Necrosis Factor-alphaABSTRACT
The treatment ideas with acupuncture for knee osteoarthritis (KOA) are explored on the base of Dongyuan needling technology. Regarding the rules of acupoint selection, Zusanli (ST 36) is predominant, the back-shu points are used for the disorders related to the invasion of exogenous factors, and the front-mu points are for the cases caused by internal injury. Besides, the xing-spring points and shu-stream points are preferred. In treatment of KOA, besides the local points, the front-mu points, i.e. Zhongwan (CV 12), Tianshu (ST 25) and Guanyuan (CV 4), are selected specially to tonifying the spleen and stomach. The earth points and acupoints on the earth meridians (i.e. Yinlingquan [SP 9], Xuehai [SP 10], Liangqiu [ST 34], Dubi [ST 35], Zusanli [ST 36] and Yanglingquan [GB 34]) are optional to coordinate yin and yang, essence and qi , and regulate the qi movement of spleen and stomach. The shu-stream points of liver, spleen and kidney meridians (Taichong [LR 3], Taibai [SP 3] and Taixi [KI 3]) are chosen to promote meridian circulation and regulate zangfu functions.
Subject(s)
Humans , Osteoarthritis, Knee , Acupuncture Therapy , Meridians , Acupuncture Points , SpleenABSTRACT
BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).
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Large-scale populations in the world have been vaccinated with COVID-19 vaccines, however, breakthrough infections of SARS-CoV-2 are still growing rapidly due to the emergence of immune-evasive variants, especially Omicron. It is urgent to develop effective broad-spectrum vaccines to better control the pandemic of these variants. Here, we present a mosaic-type trimeric form of spike receptor-binding domain (mos-tri-RBD) as a broad-spectrum vaccine candidate, which carries the key mutations from Omicron and other circulating variants. Tests in rats showed that the designed mos-tri-RBD, whether used alone or as a booster shot, elicited potent cross-neutralizing antibodies against not only Omicron but also other immune-evasive variants. Neutralizing antibody titers induced by mos-tri-RBD were substantially higher than those elicited by homo-tri-RBD (containing homologous RBDs from prototype strain) or the inactivated vaccine BBIBP-CorV. Our study indicates that mos-tri-RBD is highly immunogenic, which may serve as a broad-spectrum vaccine candidate in combating SARS-CoV-2 variants including Omicron.
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The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the "immune-escape" Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.
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@#AIM: To explore the safety and efficacy of air tamponade in the closure of large idiopathic macular holes(IMHs).<p>METHODS: A retrospective study. Nine eyes of eight patients with large IMH were admitted to our hospital from June 2017 to may 2018. Mean macular hole(MH)minimum diameter >700 μm and mean MH basal diameter >1 300 μm. All the patients were underwent 25G phacovitrectomy, internal limiting membrane flaptuck, and sterilized air tamponade in the vitreous cavity. With a mean follow up of 12mo, the best-corrected visual acuity(BCVA)and macular hole closure were compared before and after operation.<p>RESULTS: At the last follow up, all the patients obtained MH closure. The SD-OCT showed that the postoperative MH closure rate was 100%(9/9). Postoperative BCVA improved significantly compared with the preoperative(0.83±0.26 <i>vs</i> 1.27±0.28), the difference was statistically significant(<i>P</i>=0.007). No complications occurred during and after the operation.<p>CONCLUSION: Sterilized air tamponade might provide a safe and efficient effect on the closure of large IMHs.
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OBJECTIVE@#The objective of this study is to determine whether coronary atherosclerotic plaque composition is associated with cardiovascular disease (CVD) risk in Chinese adults.@*METHODS@#We performed a cross-sectional analysis in 549 subjects without previous diagnosis or clinical symptoms of CVD in a community cohort of middle-aged Chinese adults. The participants underwent coronary computed tomography (CT) angiography for the evaluation of the presence and composition of coronary plaques. CVD risk was evaluated by the Framingham risk score (FRS) and the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score.@*RESULTS@#Among the 549 participants, 267 (48.6%) had no coronary plaques, 201 (36.6%) had noncalcified coronary plaques, and 81 (14.8%) had calcified or mixed coronary plaques. The measures of CVD risk including FRS and ASCVD risk score and the likelihood of having elevated FRS significantly increased across the groups of participants without coronary plaques, with noncalcified coronary plaques, and with calcified or mixed coronary plaques. However, only calcified or mixed coronary plaques were significantly associated with an elevated ASCVD risk score [odds ratio (OR) 2.41; 95% confidence interval (CI) 1.09-5.32] compared with no coronary plaques, whereas no significant association was found for noncalcified coronary plaques and elevated ASCVD risk score (OR 1.25; 95% CI 0.71-2.21) after multivariable adjustment.@*CONCLUSION@#Calcified or mixed coronary plaques might be more associated with an elevated likelihood of having CVD than noncalcified coronary plaques.
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Female , Humans , Male , Middle Aged , Asian People , Cardiovascular Diseases , Epidemiology , Computed Tomography Angiography , Odds Ratio , Plaque, Atherosclerotic , Diagnostic Imaging , Epidemiology , Risk FactorsABSTRACT
Objective To summarize the clinical experience of bortezomib-based treatment for Waldenstr?m macroglobu-linemia and evaluate the therapeutic efficacy and safety .Methods The clinical data were collected for 15 patients with Waldenstr?m macroglobulinemia receiving bortezomib-based treatment from December 2008 to October 2015 .Three therapeutic regimens included BD (bortezomib and dexamethasone) in one case ,RBD (bortezomib ,rituximab and dexamethasone) in three cases and BCD (bortezomib ,dexamethasone and cyclophosphamide) in eleven cases .Responses ,adverse reactions and survival analysis were evaluated respectively .Results The overall response rate and major response rate were 93 .3% and 80% inclu-ding CR 1 case ,VGPR 2 cases ,PR 9 cases and MR 2 cases .The common adverse events included gastrointestinal (53 .3% ) , leukopenia (20% ) ,infection (20% ) and peripheral neuropathy (26 .7% ) .After a median follow-up of 21 (3-85) months ,the median PFS (progression-free survival) time was 21 (3-36) months and 1 year PFS rate was 83 .3% .Survival analysis showed that two prognostic risk factors related to PFS were high-risk group based on international prognostic scoring system for WM (IPSSWM )(P=0 .015) and the low response to treatment (< PR) (P=0 .024) .Conclusion Bortezomib-based therapeutic regimensexhibited significant efficacyfor patients with WM .IPSSWM and the responses to treatment can be usedto monitor the disease progression and evaluate the therapeutic result .
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OBJECTIVES: We explored the feasibility of reconstructing tracheal wall defects with a mesh patch fashioned from a nickel-titanium shape-memory alloy. METHODS: A tracheal wall defect was first constructed surgically by resecting the anterior half of the tracheal wall between the second and sixth tracheal rings. The defect was reconstructed in 8 experimental animals by replacing the resected tracheal mucosa and tracheal cartilage with a pedicle skin flap, which was then enclosed in the mesh patch. In 4 control animals, only a pedicle skin flap with strap muscles was used in the reconstruction procedure. The performance of the animals was observed after surgery. At the end of the experiments, the reconstructed segment was harvested for anatomic evaluation. RESULTS: In the experimental group, 1 animal died 5 days after the operation. Endoscopic and anatomic examination of the 7 animals that survived the observation period showed that the reconstructed trachea was stable, with sufficient airway space for breathing. All 4 control animals died after the operation. After observing successful completion of this operation in animals, we successfully used this method to repair a tracheal wall defect in a human victim of a traffic accident. CONCLUSIONS: Tracheal defects can be successfully reconstructed by use of a mesh patch of nickel-titanium shape-memory alloy as an extraluminal stent--a method that avoids complications associated with intraluminal stents.
Subject(s)
Surgical Mesh , Trachea/surgery , Accidents, Traffic , Alloys , Animals , Cricoid Cartilage/injuries , Cricoid Cartilage/surgery , Dogs , Dyspnea/etiology , Dyspnea/surgery , Feasibility Studies , Female , Fractures, Cartilage/surgery , Humans , Male , Models, Animal , Nickel , Random Allocation , Thyroid Cartilage/injuries , Thyroid Cartilage/surgery , Titanium , Trachea/injuries , Tracheotomy , Young AdultABSTRACT
<p><b>OBJECTIVE</b>To evaluate the immunogenicity of the decellularized laryngeal scaffold.</p><p><b>METHODS</b>Twelve perfused, decellularized laryngeal scaffolds were obtained from rabbits through common carotid artery perfusion with detergents. The twelve decellularized laryngeal scaffolds and the twelve fresh larynxes were then implanted in para-laryngeal muscles of rabbits and harvested after two weeks, four weeks, twelve weeks and twenty-four weeks, respectively. Macroscopic view, histological examination and lymphocyte infiltration test were performed.</p><p><b>RESULTS</b>The decellularized larynxes were implanted and preserved the laryngeal extracellular matrix and laryngeal architecture. The decellularized larynx did not show obvious immunological rejection after implanted into the para-laryngeal muscles of the recipient rabbits. The volume of implanted larynx became smaller but retained cartilage scaffold. The larynxes in the control group presented the serious immunological rejection and the majority tissues of the larynxes were disintegrated and substituted by the fibrous connective tissues after four weeks. The peripheral tissues were damaged and necrotic at different degrees. The quantity of the lymphocyte infiltration in the control group was higher than that in the experiment group and the result had the statistical significance (P < 0.01).</p><p><b>CONCLUSIONS</b>Perfused, decellularized technique can construct a low immune laryngeal cartilage scaffold which could be a satisfactory material for laryngeal repair.</p>
Subject(s)
Animals , Female , Male , Rabbits , Cartilage , Cell Biology , Cells, Cultured , Graft Rejection , Allergy and Immunology , Larynx, Artificial , Lymphocytes , Allergy and Immunology , Prosthesis Implantation , Tissue Engineering , Methods , Tissue ScaffoldsABSTRACT
<p><b>OBJECTIVE</b>To prepare a decellularized whole laryngeal scaffold by utilizing a perfusion-decellularized technique, reseed cells on it, and construct decellularized laryngeal muscles.</p><p><b>METHODS</b>Perfusion decellularized larynxes were obtained by common carotid arterious perfusion with detergents. Then they were performed by macroscopic view, histological examination, scanning electron microscopy (SEM) and cartilage viability. Decellularized laryngeal scaffold were then reseeded with inducted mesenchymal stem cells (MSCs). Composites were transferred into greater omentums of rabbits after one day's adherence and harvested after eight weeks. Macroscopic view, histological examination and immunohistochemistry were performed.</p><p><b>RESULTS</b>Perfusion larynxes became transparent after two hours. Histology and SEM indicated that perfusion method showed better decullularized effect. More vintages and collagen fibers but no intact cell or nuclei were retained in the decellularized matrix. Porosity measured by Image pro plus 6.0 was 80.4% +/- 3.2% (x +/- s). Chondrocyte vitality assay indicated chondrocyte vitality rate in the perfusion group was 86.9% +/- 1.5%. After eight weeks, vascularization formed and integrated cartilage frameworks still remained. Histological examination could clearly show the presence of muscle bundles and vessels. Immunohistochemical examination indicated that sarcomeric-alpha actin expressed positively in corresponding areas.</p><p><b>CONCLUSIONS</b>It is feasible to reseed MSCs into the decellularized laryngeal muscle matrix for constructing tissue-engineered laryngeal muscles. This in vivo maturation into the omentum could be the first step before in situ implantation of the construct.</p>
Subject(s)
Animals , Rabbits , Extracellular Matrix , Feasibility Studies , Laryngeal Muscles , Cell Biology , Physiology , Larynx, Artificial , Regeneration , Tissue Engineering , Methods , Tissue ScaffoldsABSTRACT
<p><b>OBJECTIVE</b>To study the effect of saikosaponins, the active ingredients of Bupleurum chinense DC, on epileptic seizure and EEG of pentetrazole (PTZ)-induced chronic kindling rats.</p><p><b>METHODS</b>Forty-eight healthy Sprague-Dawley rats were randomly divided into 6 equal groups, namely the blank control group, normal saline (NS) group, sodium valproate (VPA) group, and 3 saikosaponins groups of high, medium and small doses. Except those in the blank control group, the rats in the other groups were all given different treatments as specified prior to intraperitoneal PTZ injection to induce kindling on a daily basis for 4 consecutive weeks. Epileptic seizures of the rats were recorded during the treatment and EEG recorded at the end of the treatments.</p><p><b>RESULTS</b>Seizure frequency in the 3 saikosaponins groups decreased 2 weeks later, which was especially obvious in the high-dose group (P<0.05). The kindling rate was significantly lower in high-dose saikosaponins group than in the other treatment groups after 4 weeks of the treatment (P<0.05), with also less intense seizure onset (P<0.01) and differences in the wave form of EEG.</p><p><b>CONCLUSION</b>Saikosaponins can inhibit PTZ-induced epileptic seizure in kindling rats and antagonize the kindling effect of PTZ.</p>
