Scalable Dual In Situ Synthesis of Polyester Nanocomposites for High-Energy Storage.

Incorporating ultralow loading of nanoparticles into polymers has realized increases in dielectric constant and breakdown strength for excellent energy storage. However, there are still a series of tough issues to be dealt with, such as organic solvent uses, which face enormous challenges in scalable preparation. Here, a new strategy of dual in situ synthesis is proposed, namely polymerization of polyethylene terephthalate (PET) synchronizes with growth of calcium borate nanoparticles, making polyester nanocomposites from monomers directly. Importantly, this route is free of organic solvents and surface modification of nanoparticles, which is readily accessible to scalable synthesis of polyester nanocomposites. Meanwhile, uniform dispersion of as ultralow as 0.1 wt% nanoparticles and intense bonding at interfaces have been observed. Furthermore, the PET-based nanocomposite displays obvious increases in both dielectric constant and breakdown strength as compared to the neat PET. Its maximum discharged energy density reaches 15 J cm-3 at 690 MV m-1 and power density attains 218 MW cm-3 under 150 Ω resistance at 300 MV m-1, which is far superior to the current dielectric polymers that can be produced at large scales. This work presents a scalable, safe, low-cost, and environment-friendly route toward polymer nanocomposites with superior capacitive performance.

Acupuncture promotes neurological recovery and regulates lymphatic function after acute inflammatory nerve root injury.

Aims: To investigate the therapeutic effect of acupuncture on acute inflammatory nerve root injury by regulating lymphatic function. Main methods: A mouse model of L5 nerve root compression was used to simulate acute nerve root injury. After modeling, acupuncture treatment was given each day for one week. Pain thresholds were assessed before and after modeling and treatment. Immunofluorescence staining was performed to observe the distribution astrocytes and neurons in the lumbar spinal cord, the innervation rate of neuromuscular junctions (NMJs), lymphatic endothelial cells (LECs) of lumbar aortic lymph nodes, and the percentage of M1 macrophages. The number of each type of immune cells in the lumbar aortic lymph nodes (LALNs) was measured by flow cytometry. Key findings: The model group showed a significant decrease in pain threshold in the affected lower limb, while acupuncture treatment was able to significantly increase it. Acupuncture significantly repaired astrocytes and neurons in the lumbar spinal cord of the compressed segment, increased the innervation rate of nerve endings at NMJs, reduced LECs in the LALNs, reduced the proportion of M1 macrophages in the LALNs, and significantly reduced mononuclear neutrophils and monocytic neutrophils. Significance: Acupuncture can reduce pain, promote nerve repair in mice with acute nerve root injury, and suppress immune responses in lumbar aortic lymph nodes.

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes.

Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

Chronic spinal cord compression associated with intervertebral disc degeneration in SPARC-null mice.

Chronic spinal cord compression (CSCC) is induced by disc herniation and other reasons, leading to movement and sensation dysfunction, with a serious impact on quality of life. Spontaneous disc herniation rarely occurs in rodents, and therefore establishing a chronic spinal cord compression (CSCC) animal model is of crucial importance to explore the pathogenesis and treatment of CSCC. The absence of secreted protein, acidic, and rich in cysteine (SPARC) leads to spontaneous intervertebral disc degeneration in mice, which resembles human disc degeneration. In this study, we evaluated whether SPARC-null mice may serve as an animal model for CSCC. We performed rod rotation test, pain threshold test, gait analysis, and Basso Mouse Scale score. Our results showed that the motor function of SPARC-null mice was weakened, and magnetic resonance images revealed compression at different spinal cord levels, particularly in the lumbar segments. Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes, activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype; it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway. Notably, these findings are characteristics of CSCC. Therefore, we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.

[Re-mineralization ability of Galla chinensis extracts on root carious lesions with or without non-collagen proteins].

OBJECTIVE: To evaluate the re-mineralization ability of Galla Chinensis extracts (GCE) on two artificial carious lesions in bovine root de-mineralized in vitro. METHODS: Fourteen bovine root blocks were divided into two parts from buccal to lingual direction. The mesial blocks were treated with a demineralization solution and the distant blocks were treated with another demineralization solution. Two specimens from each group were selected randomly and examined with polarization microscope (PLM). After all blocks were demineralized, half surface of the demineralized zone was covered and the another half was treated with 0.5% NaCl to extract soluble dentin phosphate protein (S-DPP). Then all specimens were submitted to pH-cycling for one week. In the first four days, all specimens were treated with GCE for 21 h and with demineralization solution for 3 h. In the remaining three days, all specimens were treated with GCE. The re-mineralization ability of GCE on the specimens was evaluated by laser scanning confocal microscope (LSCM). RESULTS: There existed intact surface layers on subsurface lesions but no surface layers were produced on erosive lesions. The re-mineralization ability of GCE on erosive lesions improved significantly with the treatment of 0.5% NaCl solution (P < 0.05). But it had no significant effect on subsurface lessions. CONCLUSION: Extraction of S-DPP with 0.5% NaCl can improve the re-mineralization ability of GCE on root caries with erosive lesions. This finding supports the proposition that Galla Chinesis may be a promising anti-caries natural medicine in the future.

Analysis of serum homocysteine concentration in patients less than 35 years of age with polycystic ovary syndrome and hyperandrogenism.

OBJECTIVES: An increase in homocysteine (Hcy) concentration is closely related to polycystic ovary syndrome (PCOS). This study aimed to further explore serum homocysteine concentration and its influencing factors in clinically young (≤ 35 years) patients with PCOS and hyperandrogenism. MATERIAL AND METHODS: An electrochemical immunoassay was used to investigate the changes in serum homocysteine and related indexes in clinically young patients with PCOS and hyperandrogenism, and the results were statistically analyzed. RESULTS: Serum homocysteine concentration in clinically young patients with PCOS and hyperandrogenism (n = 208) was found to be significantly higher than in the control group (n = 663) (15.21 ± 9.99 vs. 12.56 ± 7.20 µmol/L, p < 0.0001), and the total testosterone concentration (1.65 ± 0.68 ng/mL) was higher in the PCOS group than in the control group (1.52 ± 0.58 ng/mL), p = 0.007. The receiver operating characteristic curve showed that the area under the curve of homocysteine in predicting PCOS was 0.606, and the 95% confidence interval (CI) was 0.563-0.650 (p < 0.001). The homocysteine concentrations of the two groups were graded, and it was found that the percentage of patients with homocysteine levels > 15 µmol/L was 26.92% in the PCOS group and 19.15% in the control group; the difference between the two groups was statistically significant (p = 0.0143). The serum homocysteine levels of the two groups were higher in obese patients than in non-obese patients (normal weight vs. overweight), and the difference in the control group was statistically significant. CONCLUSIONS: Serum homocysteine concentration in clinically young patients with PCOS and hyperandrogenism is elevated, so hyperhomocysteinemia can be used as one of the potential indicators of PCOS. In the process of the diagnosis and treatment of patients with PCOS, serum homocysteine concentration and body weight should both be considered.

Inhibitory effect of YQHYRJ recipe on osteoblast differentiation induced by BMP-2 in fibroblasts from posterior longitudinal ligament of mice.

Ossification of posterior longitudinal ligament (OPLL) is a common disease in Asian countries. Osteoblast differentiation in posterior longitudinal ligamentous fibroblast is a pathologic basis of OPLL. Nowadays, an effective pharmacotherapy for OPLL is still hunted for. YQHYRJ Recipe (YQHYRJ) is designed based on traditional Chinese medicine (TCM) theories, and previous clinic trials reported its effect on relieving syndromes of cervical spondylopathy. To clarify the YQHYRJ effect of OPLL on a cellular level, we induced mice fibroblasts from posterior longitudinal ligaments to differentiate into osteoblasts by human recombinant BMP-2, and treated them with YQHYRJ and its three sub-compounds: YQ, HY and RJ. YQHYRJ and the sub-compounds reduced the increase of fibroblast proliferation, mineralization, type I collagen secretion induced by BMP-2 via MTT, alizarin red staining and immunochemical examination. Moreover, these agents inhibited BMP-2 induced upregulation of ossification-related genes ALP, Col I and OC as well as BMP signal molecules Smad1, Smad 5 and Runx2 mRNA expression. These results suggested YQHYRJ to be effective in inhibiting osteoblast differentiation induced by BMP-2 in fibroblasts from posterior longitudinal ligament. YQHYRJ might be a promising medicine for preventing OPLL disease.

The osteogenetic effect of astragaloside IV with centrifugating pressure on the OCT-1 cells.

Astragaloside IV (ASI), a pure compound derived from Radix Astragali, is commonly used in degenerative bone diseases such as osteoporosis. Our previous study identified in vivo the osteogenetic effect of Fu Fang Qi She Pills (FFQSP), a Chinese herbal formula containing Radix Astragali from which ASI was extracted. In this study, we investigated the osteogenetic effects of ASI under the conditions of centrifugating pressure on OCT-1 cells. These preosteoblasts were grown in 3D-culture, and treated with ASI at 50 micromol/l with centrifugation at 200 rpm, 500 rpm for 3 and 5 days. Morphocytological examination, morphometry of alkaline phosphatases (ALP) staining was performed. Expression of type I collagen (Col I) was detected by immunocytochemistry assays. ALP, Col1a2, Osteocalcin (OC), and runt-related transcription factor-2 (Runx2) mRNA expression were determined via real-time PCR. The results showed ASI plus 500 rpm for 3 days and ASI plus 200 rpm for 5 days significantly induced osteogenesis related protein and gene expression. We concluded that ASI would promote osteogenesis when cells of preosteoblast OCT-1 were subjected to proper centrifugating pressure and a pertinent period of time.

Herb formula "Fufangqishe-Pill" prevents upright posture-induced intervertebral disc degeneration at the lumbar in rats.

Degeneration of the lumbar spine plays an important role in most chronic low back pain. Prevention of lumbar intervertebral disc (IVD) degeneration is therefore a high research priority. Both our previous multicenter clinical trials and pharmacological research showed that Fufangqishe-Pill (FFQSP), a newly patented traditional Chinese medicine, could effectively relieve the symptoms of neck pain and prevent cervical degeneration. To clarify the effect of FFQSP on lumbar IVD degeneration, we applied a lumbar IVD degeneration rat model induced by prolonged upright posture. Pretreatment of FFQSP for one month prevented the histological changes indicating IVD disorganization; increased type II-collagen level, decreased type X-collagen protein level, and increased Col2alpha1 mRNA expression at all time points; and decreased Col10alpha1, matrix metalloproteinase (MMP)-3, MMP13, and Interleukin (IL)-1beta mRNA expression induced by upright posture for 7 and 9 months. These results suggest that FFQSP prevents lumbar IVD degeneration induced by upright posture. FFQSP is a promising medicine for lumbar IVD degeneration disease.

Muscone protects vertebral end-plate degeneration by antiinflammatory property.

Most chronic neck pain is the result of degeneration of the cervical spine. IL-1beta may play an important role in intervertebral disc degeneration. This being the case, inhibiting IL-1beta could provide a therapeutic approach for reducing or preventing disc degeneration. Muscone reportedly relieves pain and suppresses inflammation. Therefore, we asked whether muscone, a potent antiinflammatory agent, could reduce proinflammatory cytokines in vitro (end-plate cartilage cultures) and end-plate degeneration in vivo (a rat model that induces intervertebral disc degeneration). In vitro, muscone reversed IL-1beta-induced upregulation of IL-1beta, tumor necrosis factor alpha, cyclooxygenase 2, inducible nitric oxide synthase, matrix metalloproteinase 13, aggrecanase 2, and nitric oxide and downregulation of Col2alpha1 and aggrecan. Pretreatment with muscone (6.25, 12.5, 25 mumol/L) inhibited the IL-1beta-induced phosphorylation of extracellular signal-regulated kinases 1/2 and c-Jun N-terminal kinase in a dose-dependent manner. In vivo, muscone inhibited the expression of prostaglandin E2, 6-keto-prostaglandin F1alpha, IL-1beta, and tumor necrosis factor alpha and recovered the structural distortion of the degenerative disc. Our findings suggest muscone is a promising agent for treating intervertebral disc degeneration through its antiinflammatory effects.

[Effects of Qishe Pill on vertebral hyperostosis induced by upright posture in rats].

OBJECTIVE: To observe the effects of Qishe Pill, a compound traditional Chinese herbal medicine, on lumbar vertebral bone formation induced by long-time upright posture in rats and to investigate the potential mechanism. METHODS: Thirty SD rats were randomly divided into normal control group, untreated group and Qishe Pill group. The rats in normal control group received no treatment and were raised in normal cages. The rats in untreated group and Qishe Pill group were cut off forelimbs by operation so as to be forced to adopt an upright posture for 8 months to induce hyperostosis. Rats in the Qishe Pill group were intragastrically administered with Qishe Pill at a dose of 5 g/(kg x d) for 1 month. All rats were sacrificed at the 9th month after surgery and all lumbar vertebrae were harvested for detection. Safranin O/fast green staining and picrosirius red staining were used to observe pathological changes. Expressions of type I collagen (ColI), type X collagen (ColX), vascular endothelial growth factor (VEGF) and transforming growth factor beta1 (TGF-beta1) in the 5th lumbar vertebra (L(5)) were detected by immunohistochemical method. Expressions of type I collagen alpha2 (Col1alpha2), type X collagen alpha1 (Col10alpha1), TGF-beta1, and VEGF and runt-related transcription factor 2 (Runx2) mRNAs in L(1)-L(3) were detected by real-time fluorescent quantitation reverse transcription-polymerase chain reaction. RESULTS: Safranin O/fast green staining showed that in the untreated group, non-matrix components increased at marginal lumbar vertebra and intervertebral disc junction, and hyperostosis appeared. However, no obvious change was observed in the normal control group. Non-matrix components decreased at the same location in Qishe Pill group as compared with the untreated group. Picrosirius red staining showed compact collagens at marginal lumbar vertebra and intervertebral disc junction in the normal control group, however, Col I and ColX increased at the same location in the untreated group. In the Qishe Pill group, it showed more compact collagens, especially ColI. Compared with normal control group, expressions of ColX, VEGF and TGF-beta1 were increased at marginal lumbar vertebra and intervertebral disc junction in the untreated group. ColX and VEGF expressions decreased in the Qishe Pill group as compared with the untreated group. Col10alpha1 and Runx2 mRNA expressions were down-regulated by Qishe Pill (P<0.01). CONCLUSION: Qishe Pill may delay hyperostosis at marginal lumbar vertebra and intervertebral disc junction, which may be related to reducing type X collagen and Runx2 expressions.

Modulation of hepatic lipidome by rhodioloside in high-fat diet fed apolipoprotein E knockout mice.

BACKGROUND: Rhodioloside is a glucoside of tyrosol isolated from Rhodiola rosea. However, its regulating effect on hepatic dyslipidemia of atherogenic mice has rarely been studied. PURPOSE: The specific aims of current study included to clarify lipidomic perturbation in liver tissues of apolipoprotein E deficient (apoE-/-) mice fed with high-fat diet, and to examine the effects of rhodioloside against atherosclerosis and dyslipidemia. STUDY DESIGN: The comparisons of hepatic lipidome were executed between wide type (WT) mice fed with normal diet (NDC) and apoE-/- mice fed with high-fat diet (Model), WT mice fed with high-fat diet (HFDC) versus the model mice, as well as the model mice versus rhodioloside-treated atherosclerotic mice. METHODS: Ultra high performance liquid chromatography coupled with a Q exactive hybrid quadrupole-orbitrap mass spectrometry (UPLC-MS/MS) was employed to provide an unbiased and simultaneous measurement of individual lipid species in liver tissues. RESULTS: Multivariate statistical analysis derived from LC-MS spectra revealed that high-fat diet and apoE deficiency caused a series of disturbances on glyerolipid metabolism, glycerophospholipid metabolism and sphingolipid metabolism. Rhodioloside administration showed atheroprotective effects on the apoE-/- mice with regulating the levels of 1 phosphatidylcholine, 2 phosphatidylserines, 5 alkyldiacylglycerols and 3 alkenyldiacylglycerols back to normal. In particular, PC (4:0/15:0) was positively associated with high-density lipoprotein cholesterol in blood, both of which could be ameliorated by rhodioloside. CONCLUSION: Our results identified the abnormal hepatic lipids in atherosclerosis progression that could efficiently improved by rhodioloside. These lipids contributed to biological understanding of atherogenic dyslipidemia in liver and could also served as sensitive indicators for drug target screening.

[Preventive and therapeutic effects of Yiqi Huayu Recipe on degeneration of articular cartilage in rats with osteoarthritis].

OBJECTIVE: To study the efficacy and possible mechanism of Yiqi Huayu Recipe (YQHYR), a compound traditional Chinese herbal medicine, in preventing and treating degeneration of the articular cartilage in rats with osteoarthritis (OA). METHODS: A total of 90 one-month-old SD rats were randomly divided into normal control group, untreated group and YQHYR group, with 30 rats in each group. The osteoarthritis was induced by shoulder disarticulation plus upright posture in rats. The rats in YQHYR group were treated with YQHYR at 5-, 7- and 9-month old (4, 6 and 8 months after the surgery) for one month. Ten rats in each subgroup were sacrificed at 6-, 8- and 10-month old (5, 7 and 9 months after the surgery) respectively and the knee joint samples were harvested for detection. Safranin-O/fast green staining was performed to examine the morphology of articular cartilage. The expressions of type II collagen (Col2A1), aggrecan-1 (Agc1), matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNAs were evaluated by real-time fluorescent quantitation polymerase chain reaction. RESULTS: Histological analysis showed that the structure of articular cartilage was seriously destroyed in rats in the untreated group. On the contrary, the degenerative changes of the articular cartilage in the YQHYR group were dropped off. Real-time fluorescent quantitation polymerase chain reaction showed that expressions of Agc1, TIMP-1 and Col2A1 mRNAs were up-regulated in 6- and 10-month-old rats in the YQHYR group as compared with those in the untreated group (P<0.01, P<0.05), but there was no significant difference in expression of MMP-13 mRNA between the YQHYR group and the untreated group. The expression of Agc1 mRNA was up-regulated and the expression of MMP-13 mRNA was down-regulated in the 8-month-old rats in YQHYR group as compared with those in the untreated group (P<0.01). CONCLUSION: YQHYR can promote the synthesizing of aggrecan and type II collagen in chondrocytes and delay articular cartilage degradation in OA rats.

[Mechanism of Yiqi Huayu Bushen recipe in treating cervical syndrome in rats with qi deficiency, blood stasis and kidney deficiency].

OBJECTIVE: To explore the mechanism of Yiqi Huayu Bushen Recipe (YHBR), a compound traditional Chinese herbal medicine, in treating cervical syndrome (CS) with qi deficiency, blood stasis and kidney deficiency in rats. METHODS: A total of 30 three-month-old female Sprague-Dawley rats were randomly divided into normal control group, untreated group and YHBR group; there were ten rats in each group. The rat model of cervical syndrome with qi deficiency, blood stasis and kidney deficiency was established by combining disease and syndrome models. After one-month YHBR treatment in YHBR group, all rats were sacrificed. Serum, plasma and cervical intervertebral discs were detected and observed by radio-immunology, histopathology, immunohistochemistry, etc. RESULTS: Compared with those in the normal control group, rats in the untreated group showed obvious signs of deficiency in vital energy, such as tiredness, ptosis, few movement, bluish-purple tongue and tail and weight loss; the weight of uterus and appendages, and the ratio of cyclic adenosine monophosphate/cyclic guanosine monophosphate were decreased; hemorheological parameters and the expression of alpha-granular membrane protein (CD62p) were increased; the content of serum estradiol was decreased. YHBR could improve the above indexes except for the weight of uterus and appendages. HE staining showed annulus fibrosus with cracks, diminish of pulposus nucleus, and decrease in the height of intervertebral disc and the thickness of end-plate in the untreated group; and YHBR could improve the changes of cervical intervertebral discs, but no obvious changes in end-plate. Type II collagen protein (Col2a1)was distributed in every part of the annulus fibrosus in normal control group, but was decreased in untreated group; YHBR could increase Col2a1 expression in annulus fibrosus as compared with the untreated group. The expressions of Col2a1 and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNAs were decreased in untreated group as compared with the normal control group (P<0.01); the expressions of Col2a1 and TIMP-1 mRNAs were higher and matrix metalloproteinase-13 mRNA was lower in the YHBR group than those in the untreated group (P<0.05, P<0.01). CONCLUSION: YHBR may improve the condition of cervical syndrome with qi deficiency, blood stasis and kidney deficiency by regulating immune system, coagulation system and endocrine system, and delay the degeneration of cervical intervertebral disc by regulating extracellular matrix and metalloproteases in intervertebral disc.

MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of MK-801 and its effect on lesion volume in rat models of acute brain injury. DATA SOURCES: Key terms were "stroke", "brain diseases", "brain injuries", "brain hemorrhage, traumatic", "acute brain injury", "dizocilpine maleate", "dizocilpine", "MK-801", "MK801", "rat", "rats", "rattus" and "murine". PubMed, Cochrane library, EMBASE, the China National Knowledge Infrastructure, WanFang database, the VIP Journal Integration Platform (VJIP) and SinoMed databases were searched from their inception dates to March 2018. DATA SELECTION: Studies were selected if they reported the effects of MK-801 in experimental acute brain injury. Two investigators independently conducted literature screening, data extraction, and methodological quality assessments. OUTCOME MEASURES: The primary outcomes included lesion volume and brain edema. The secondary outcomes included behavioral assessments with the Bederson neurological grading system and the water maze test 24 hours after brain injury. RESULTS: A total of 52 studies with 2530 samples were included in the systematic review. Seventeen of these studies had a high methodological quality. Overall, the lesion volume (34 studies, n = 966, MD = -58.31, 95% CI: -66.55 to -50.07; P < 0.00001) and degree of cerebral edema (5 studies, n = 75, MD = -1.21, 95% CI: -1.50 to -0.91; P < 0.00001) were significantly decreased in the MK-801 group compared with the control group. MK-801 improved spatial cognition assessed with the water maze test (2 studies, n = 60, MD = -10.88, 95% CI: -20.75 to -1.00; P = 0.03) and neurological function 24 hours after brain injury (11 studies, n = 335, MD = -1.04, 95% CI: -1.47 to -0.60; P < 0.00001). Subgroup analysis suggested an association of reduction in lesion volume with various injury models (34 studies, n = 966, MD = -58.31, 95% CI: -66.55 to -50.07; P = 0.004). Further network analysis showed that 0-1 mg/kg MK-801 may be the optimal dose for treatment in the middle cerebral artery occlusion animal model. CONCLUSION: MK-801 effectively reduces brain lesion volume and the degree of cerebral edema in rat models of experimental acute brain injury, providing a good neuroprotective effect. Additionally, MK-801 has a good safety profile, and its mechanism of action is well known. Thus, MK-801 may be suitable for future clinical trials and applications.

The efficacy of the traditional Chinese medicine Jia Wei Niu Bang Zi granule combined with methotrexate in treating active rheumatoid arthritis: A multicenter, randomized, double-blinded controlled clinical trial.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic systemic and autoimmune inflammatory disease ending with the destruction of joints. Current therapies can relieve RA symptoms, but some also bring severe adverse events. Therefore, an effective and safe therapeutic strategy remains to be created to benefit patients with RA by large. Jia Wei Niu Bang Zi granule (NBZG) consisting of RA-fighting Chinese herbals has been used in Longhua Hospital in the last several decades. NBZG has potential therapeutic effect on RA, which should be evaluated by larger sample clinical trial. METHODS: A multicenter, randomized, double-blind, placebo-controlled clinical trials will be conducted to determine the efficiency of NBZG in pain relief and joint protection. A total of 120 patients with active RA will be enrolled, and treated with NBZG or placebo for 12 weeks. The primary outcome measurements include rate of American College of Rheumatology (ACR) 50 at 12 weeks' treatment. The 2nd outcome measurements include rate change of ACR20, ACR70, the disease activity score (DAS) 28, 36-item Short-Form Health Survey Questionnaire, Health Assessment Questionnaire - Disability Index, score changes of Patient Assessment of Arthritis Pain, Patient Global Assessment of Arthritis, and the Athens insomnia scale at the same time points. DISCUSSION: Although NBZG has shown efficacy in treating RA in Longhua Hospital for decades, the universality of this efficacy needs evaluated. The results of this trial will provide a convincing evidence about NBZG's efficacy in treating active RA in a large population. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03173040 (registered on May 30, 2017).

[Mechanism of Yiqi Huayu Bushen Recipe in treating cervical syndrome with kidney deficiency in rats].

OBJECTIVE: To research the action mechanism of Yiqi Huayu Bushen Recipe (YHBR), a compound of traditional Chinese herbal medicine, in treating cervical syndrome (CS) with kidney deficiency in rats. METHODS: A total of 30 three-month-old female Sprague-Dawley rats were randomly divided into normal control group, CS with kidney deficiency model group (untreated group) and YHBR group, with 10 rats in each group. Rats in the normal control group received no treatment, while rats of the other two groups underwent resection of both cervical muscles and ovaries to establish the model of CS with kidney deficiency. Three months after surgery, rats in the YHBR group were intragastrically administered YHBR for one month. Another one month later, all rats were sacrificed. The content of serum estradiol (E2) was detected by radio-immunoassay; contents of plasma cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were tested, and the ratio of cAMP/cGMP was also calculated. Hemorheology was detected by Weissenberg's method; expression of alpha-granular membrane protein (CD62p) was detected by flow cytometry; HE staining was used to detect the histopathology of cervical intervertebral disc degeneration; type II collagen protein was detected by immunohistochemistry and aggrecan-1 (Agc1), type II procollagen gene, Col2a1, tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-13 (MMP-13) mRNAs were detected by fluorescent quantization polymerase chain reaction. RESULTS: Compared with the untreated group, rats in the YHBR group showed an obvious increase in serum E2 content (P<0.05), and an increase in plasma cAMP and cGMP content without significant difference; hemorheological parameters and percentage of CD62p expression were significantly decreased in the YHBR group (P<0.05, P<0.01). YHBR could improve the degeneration of cervical intervertebral discs, decrease the Miyamoto scores (P<0.05), and increase the type II collagen. The expressions of Agc1, Col2a1 and TIMP-1 mRNAs were significantly increased and MMP-13 mRNA significantly decreased in YHBR group (P<0.05, P<0.01). CONCLUSION: YHBR may improve CS with kidney deficiency and delay the degeneration of cervical intervertebral disc by regulating the immune-metabolism system, coagulation system and endocrine system.

[Establishment of a rat model of cervical syndrome with qi deficiency, blood stasis and kidney deficiency].

OBJECTIVE: To establish a rat model of cervical syndrome with qi deficiency, blood stasis and kidney deficiency. METHODS: A total of 30 three-month-old female Sprague-Dawley rats were randomly divided into normal group, cervical syndrome group and cervical syndrome with qi deficiency, blood stasis and kidney deficiency group (combined group), with 10 rats in each group. Rats in the normal group received no treatment, rats in cervical syndrome group underwent resection of cervical muscles and ligaments as unbalanced dynamic and static animal model, and rats in combined group underwent resection of both cervical muscles and ovaries, swimming and irregular diet, and injection of adrenal cortex hormone and adrenaline two and a half months after resection as combined model. The qi deficiency, blood stasis and kidney deficiency were determined by observing behaviors and physical signs of the rats, detecting the contents of plasma cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), the hemorrheology, the expression of alpha-granular membrane protein (CD62p) and the serum estradiol (E(2)) content. The aggrecan-1, type II procollagen gene (Col2a1), matrix metalloproteinases-13 (MMP-13) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNAs in cervical intervertebral discs were detected by histopathology, immunohistochemistry and real-time polymerase chain reaction. The cataplasia of the intervertebral discs was determined by detecting the histopathology, the expressions of type II collagen and type X collegen proteins, and the expressions of aggrecan-1 (Agc1), type II procollagen gene (Col2a1), matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNAs. RESULTS: Compared with those in the normal group and cervical syndrome group, the rats in the combined group were noted with obvious signs of deficiency of vital energy, such as depression, tiredness, ptosis, obvious weight loss and blue tail. And the ratio of cAMP/cGMP was decreased; the reducing viscosity was significantly up-regulated; the expression of CD62p was increased; the content of serum E(2) was decreased; the intervertebral disc structure was destructed; the cervical intervertebral disc was more seriously deteriorated. There exhibited a decrease in type II collagen protein expression, an increase in type X collagen protein expression, as well as decreases of Agc1, Col2a1 and TIMP-1 mRNA expressions in intervertebral disc, and the expression of MMP-13 mRNA was noted an increase. CONCLUSION: The rat model of cervical syndrome with qi-deficiency, blood stasis and kidney deficiency is established. Qi deficiency, blood stasis and kidney deficiency can aggravate cervical intervertebral disc degeneration.

[Establishment of a rat model of cervical syndrome with kidney deficiency].

OBJECTIVE: To establish a rat model of cervical syndrome (CS) with kidney deficiency. METHODS: A group of 30 three-month-old female Sprague-Dawley rats were randomly divided into normal control group, CS group and CS with kidney deficiency group (combined group), with 10 rats in each group. Rats in the normal control group received no treatment, rats in the CS group underwent only resection of cervical muscles and ligaments as unbalanced dynamic and static animal model, and rats in combined group underwent resection of both cervical muscles and ovaries as kidney deficiency model. Serum and cervical intervertebral discs were collected. Kidney deficiency was determined by observing the morphologic changes of uterus and appendages, detecting the weight of uterus and appendages and the content of serum estradiol (E(2)). The degeneration of intervertebral discs was determined by detecting the histopathology, the expressions of type II collagen and type X collagen proteins, and the expressions of aggrecan-1 (Agc1), type II procollagen gene (Col2a1), matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNAs. RESULTS: Compared with those in the normal control group and CS group, the rats in the combined group were noted with the uterus atrophied, the caliber of oviduct thinned, the weight of uterus and appendages diminished obviously, the content of serum E(2) decreased, cervical intervertebral disc degenerated more seriously, type II collagen protein expression decreased, type X collagen protein expression increased, Agc1 and Col2a1 mRNA expressions in intervertebral disc decreased, and the MMP-13 mRNA expression increased. CONCLUSION: The rat model of CS with kidney deficiency is established. Kidney deficiency can aggravate cervical intervertebral disc degeneration.