Nanomedicines Promote Cartilage Regeneration in Osteoarthritis by Synergistically Enhancing Chondrogenesis of Mesenchymal Stem Cells and Regulating Inflammatory Environment.

Osteoarthritis (OA) is a degenerative joint disease characterized by progressive erosion of the articular cartilage and inflammation. Mesenchymal stem cells' (MSCs) transplantation in OA treatment is emerging, but its clinical application is still limited by the low efficiency in oriented differentiation. In our study, to improve the therapeutic efficiencies of MSCs in OA treatment by carbonic anhydrase IX (CA9) siRNA (siCA9)-based inflammation regulation and Kartogenin (KGN)-based chondrogenic differentiation, the combination strategy of MSCs and the nanomedicine codelivering KGN and siCA9 (AHK-CaP/siCA9 NPs) was used. In vitro results demonstrated that these NPs could improve the inflammatory microenvironment through repolarization of M1 macrophages to the M2 phenotype by downregulating the expression levels of CA9 mRNA. Meanwhile, these NPs could also enhance the chondrogenesis of bone marrow-derived mesenchymal stem cells (BMSCs) by upregulating the pro-chondrogenic TGF-ß1, ACAN, and Col2α1 mRNA levels. Moreover, in an advanced OA mouse model, compared with BMSCs alone group, the lower synovitis score and OARSI score were found in the group of BMSCs plus AHK-CaP/siCA9 NPs, suggesting that this combination approach could effectively inhibit synovitis and promote cartilage regeneration in OA progression. Therefore, the synchronization of regulating the inflammatory microenvironment through macrophage reprogramming (CA9 gene silencing) and promoting MSCs oriented differentiation through a chondrogenic agent (KGN) may be a potential strategy to maximize the therapeutic efficiency of MSCs for OA treatment.

Antithrombin III deficiency in a patient with recurrent venous thromboembolism: A case report.

BACKGROUND: Antithrombin III (AT3) deficiency, an autosomal dominant disease, increases the likelihood of an individual developing venous thromboembolism (VTE). Long-term anticoagulation treatment is required for those suffering from AT3 deficiency. CASE SUMMARY: A man aged 23, who had a history of deep venous thrombosis (DVT), experienced recurrent pain and swelling in his right lower extremity for three days following withdrawal of Rivaroxaban. He was diagnosed with DVT and antithrombin III deficiency as genetic testing revealed a single nucleotide variant in SERPINC1 (c.667T>C, p.S223P). The patient was advised to accept long-term anticoagulant therapy. CONCLUSION: Inherited AT3 deficiency due to SERPINC1 mutations results in recurrent VTE. Patients may benefit from long-term anticoagulant therapy.

Consideration in Randomized Placebo-Controlled Trial on Neck Pain to Avoid the Placebo Effect in Analgesic Action.

Background: In neck pain treatment, many therapies are focused on etiology, while it is well-known that placebo analgesia is also present in these therapies. The specific efficacy for etiology may be underestimated by ignoring their actual placebo effect. In this study, a logistic regression analysis is used to explore the risk factors causing different placebo responses in patients with neck pain among two RCTs. The probability of the placebo effect is predicted based on these risk factors. Methods: Trial A and Trial B were similarly designed, randomized, double-/single-blind, placebo-controlled trials in patients treating neck pain with Qishe pill or Shi-style manipulation. Both studies set a placebo pill twice a day or traction for every other day as control. For further analyses on the placebo effect in neck pain management, logistic regression was used to assess subgroup-placebo interactions. The odds ratio assessed a significant influence on the placebo effect. Results: In this pooled analysis, the total number of patients recruited for these two studies was 284, of which 162 patients received placebo treatment (placebo drug or traction for every other day). No statistically significant differences are found at baseline between the participants with placebo effect and non-placebo effect in the gender, age, and disease duration except in VAS and NDI at the initial time. There are numerically more patients with placebo effect in the shorter disease duration subgroup (< 4 months [76%]), higher initial VAS subgroup (>60 mm [90%]), and worse initial NDI subgroup (>24 [72%]) compared with the gender and age subgroup. An ROC curve is established to assess the model-data fit, which shows an area under the curve of 0.755 and a 95% confidence interval of 0.677-0.830. Participants who show placebo effect after 2 weeks have significantly lower VAS scores after 4 weeks, while there is no significant difference in NDI improvement between the two groups after 4 weeks. Conclusion: Neck pain patients with shorter disease duration are more likely to overscore their pain severity, because of their less experience in pain perception, tolerance, and analgesia expectation.

Intensive blood pressure control in patients with acute type B aortic dissection (RAID): study protocol for randomized controlled trial.

BACKGROUND: Blood pressure control is an essential therapy for patients with acute type B aortic dissection (ABAD) and should be maintained throughout the entire treatment. Thus, vast majority current guidelines recommend control the blood pressure to lower than 140/90 mmHg. Theoretically, a much lower target may further decrease the risk of propagation of dissection. However, some argued that too lower blood pressure would compromise the organ perfusion. Thus, there is no unanimous optimal target for blood pressure in patients with ABAD so far. The present study aimed to investigate the optimal blood pressure target for patients with ABAD, in the hope that the result would optimize the treatment of aortic dissection (AD). METHODS: The study is a multi-center randomized controlled clinical trial. Study population will include patients with new diagnosed ABAD and hypertension. Blocked randomization was performed where intensive blood pressure control (<120 mmHg) with conventional blood pressure control (<140 mmHg) were allocated at random in a ratio of 1:1 in blocks of sizes 4, 6, 8, and 10 to 360 subjects. Interim analysis will be performed. The primary outcome is a composite in-hospital adverse outcome, including death, permanent paraplegia or semi- paralysis during the hospitalization, and renal failure requiring hemodialysis at discharge. While the secondary outcomes include the aortic size, lower extremity or visceral ischemia, retrograde propagation into aortic arch or ascending aorta, mortality in 6 months and 1 year, intensive care unit (ICU) length of stay, total length of hospital stay, creatinine level, and surgical or endovascular intervention. ETHICS AND DISSEMINATION: The study was approved by the institutional review board of Sir Run Run Shaw Hospital (approval number: 20160920-9). Informed consent will be obtained from participants or their next-of-kin. The results will be published in a peer-reviewed journal and shared with the worldwide medical community. TRIAL REGISTRATION: NCT03001739 (https://register.clinicaltrials.gov/).

One-Step Reduction and Surface Modification of Graphene Oxide by 3-Hydroxy-2-Naphthoic Acid Hydrazide and Its Polypropylene Nanocomposites.

3-Hydroxy-2-naphthoic acid hydrazide (HNH), a new reductant and modifier, was applied to reduce and modify graphene oxide (GO) in a one-step process. The obtained HNH reduced graphene oxide (HNH-rGO) was characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), Raman spectroscopy, X-ray photoelectron spectroscopic (XPS) and Fourier transform infrared spectra (FTIR). The results demonstrated that GO was successfully reduced to graphene and the surface of HNH-rGO was grafted with HNH. The interlayer space was increased from 0.751 nm to 1.921 nm, and its agglomeration was much more attenuated compared with GO. HNH-rGO/polypropylene and graphene/polypropylene composites were synthesized through melt-blending method. The viscosity was enhanced with increased addition of graphene and surface modified graphene demonstrated stronger rheological behavior improving effect than the untreated graphene.

Simultaneous Reduction and Functionalization of Graphene Oxide by 4-Hydrazinobenzenesulfonic Acid for Polymer Nanocomposites.

Graphene oxide (GO) was functionalized and reduced simultaneously by a new reductant, 4-hydrazinobenzenesulfonic acid (HBS), with a one-step and environmentally friendly process. The hydrophilic sulfonic acid group in HBS was grafted onto the surface of GO through a covalent bond. The successful preparation of HBS reduced GO (HBS-rGO) was testified by scanning electron microscope (SEM), X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared spectra (FTIR), X-ray photoelectron spectroscopic (XPS) and thermogravimetric analysis (TGA). The interlayer space of HBS-rGO was increased to 1.478 nm from 0.751 nm for GO, resulting in a subdued Van der Waals' force between layers and less possibility to form aggregations. The aqueous dispersibility of graphene was improved to 13.49 mg/mL from 0.58 mg/mL after the functionalization. The viscosity of the epoxy resin based HBS-rGO composite could be regulated by an adjustment of the content of HBS-rGO. This study provides a new and applicable approach for the preparation of hydrophilic functionalized graphene, and makes it possible for the application of graphene in some functional polymer nanocomposites, such as specialty water-based coatings.

Clinical characteristics of hand, foot and mouth disease in Harbin and the prediction of severe cases.

BACKGROUND: Hand, foot and mouth disease (HFMD) is an emerging public health problem in China, not only threatening the health of children, but also causing tremendous loss and burden to both families and society. The aim of this study was to characterize the epidemiology and clinical features of HFMD, and to understand the key factors affecting HFMD in the Harbin region to provide scientific evidence for effective prevention and control strategies. METHODS: Epidemiological and clinical information from 2379 randomly chosen cases of HFMD treated at the Harbin Center for Disease Control and Prevention from May 2008 to November 2011 were analyzed. All cases were separated into common and severe HFMD, with key factors for severe HFMD analyzed using multivariable Logistic regression. RESULTS: Among the 2379 patients, 1798 were common cases and 581 severe cases, 14 of which resulted in death. Most cases were in children younger than 5 years. Morbidity peaked in July and was higher in the surrounding country and cities than in Harbin proper. Medical expenses were significantly higher for severe than for common cases (P < 0.001). The primary clinical symptoms were fever and erythema; laboratory examination showed leucocytosis together with pneumonia, carditis, and abnormal electrocardiogram and electroencephalogram in severe cases. Multivariable Logistic regression analysis showed that the key factors for severe HFMD were age, morbidity location, morbidity area, fever duration, mouth mucosal symptoms, and abnormal serum levels of neutrophils (NEUT), hemoglobin and glucose (P < 0.05). CONCLUSIONS: To improve prognosis, reduce medical expense and prevent the development of severe cases, we should improve the epidemiological detection of HFMD to treat patients quickly. We should also closely monitor children with the EV71 virus, who present with continuous fever as well as abnormal laboratory results, from areas highly susceptible to HFMD attacks.

Preparation and properties of composites with staggered alignment of carbon nanotubes induced by electric field.

In this paper, bulk polymeric composites with staggered orientation of carbon nanotubes (CNTs) in polymer matrix were prepared by means of a macro layer-by-layer (MLBL) method, while an alternating current (AC) electric field was applied for inducing alignment of the CNTs. Test results verified that there existed a relationship between conductive capacity of the composites and orientation of the CNTs in matrix. Conductivity of the composites containing aligned CNTs represented a dependency on time and testing history on the composite specimens. Among the composites with different orientation types of CNTs in the matrices, the composite specimens including staggered orientation of CNTs in polymer matrix demonstrated the most outstanding electric conductivity and showed similar conductive properties in the two directions of the CNT alignment.

Alignment of carbon nanotubes in poly(methyl methacrylate) composites induced by electric field.

An ideal carbon nanotube (CNT) network structure in poly(methyl methacrylate) (PMMA) can be attained by adjusting simultaneously both evolution of the CNTs alignment in methyl methacrylate (MMA) monomer under alternating current (AC) electric field and polymerization of MMA. Alignment of the CNTs in liquid media is time dependent and can be enhanced by increasing suitably the voltage and frequency of the electric field. There is an optimal time window in which the ideal alignment is achieved after which the alignment degrades and the CNTs start to agglomerate due to the transverse interactions. Viscosity of the MMA increases with its polymerization, and the macro motion of CNTs stops when the viscosity is high enough. Polymerization of the MMA can be accelerated or slowed down by changing polymerization temperature and initiator concentration. If the two courses, the alignment of CNTs and the polymerization of MMA, intersect at a proper point, preferred CNTs alignment will be preserved and the prepared CNT/PMMA composites will be endowed with novel properties.

Insight into congenital absence of the portal vein: is it rare?

Congenital absence of portal vein (CAPV) was a rare event in the past. However, the number of detected CAPV cases has increased in recent years because of advances in imaging techniques. Patients with CAPV present with portal hypertension (PH) or portosystemic encephalopathy (PSE), but these conditions rarely occur until the patients grow up or become old. The patients usually visit doctors for the complications of venous shunts, hepatic or cardiac abnormalities detected by ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI). The etiology of this disease is not clear, but most investigators consider that it is associated with abnormal embryologic development of the portal vein. Usually, surgical intervention can relieve the symptoms and prevent occurrence of complications in CAPV patients. Moreover, its management should be stressed on a case-by-case basis, depending on the type or anatomy of the disease, as well as the symptoms and clinical conditions of the patient.