Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension.

BACKGROUND: Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis. Although primary prevention drugs, including non-selective ß-blockers, have effectively reduced the incidence of bleeding, their efficacy is limited due to side effects and related contraindications. With recent advances in precision medicine, precise drug treatment provides better treatment efficacy. DATA SOURCES: Literature search was conducted in PubMed, MEDLINE and Web of Science for relevant articles published up to May 2022. Information on clinical trials was obtained from https://clinicaltrials.gov/ and http://www.chictr.org.cn/. RESULTS: The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs. According to the site of action, these drugs could be classified into four classes: intrahepatic, extrahepatic, both intrahepatic and extrahepatic targets and others. All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension. CONCLUSIONS: This review classified and summarized the promising drugs, which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension, demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

MiR-122 knockdown regulates vascular smooth muscle cells phenotypic switching through enhanced FOXO3 expression.

Vascular smooth muscle cells (VSMCs) phenotypic switching is identified as enhanced dedifferentiation, proliferation, and migration ability of VSMCs, in which microRNAs have been identified as important regulators of the process. The present study is aimed to explore the pathophysiological effect of miR-122 on VSMC phenotypic modulation. Here, the result showed that the decreased miR-122 expression was found in VSMCs subjected to platelet-derived growth factor-BB (PDGF-BB) treatment. Next, we investigated the response of miR-122 knockdown in VSMCs with PDGF-BB stimulation. MiR-122 silencing showed increased proliferation and migration capability, whereas attenuated the differentiation markers expression. The above results were reversed by miR-122 overexpression. Finally, we further demonstrated that FOXO3 was an important target for miR-122. Collectively, we demonstrated that miR-122 silencing promoted VSMC phenotypic modulation partially through upregulated FOXO3 expression that indicated miR-122 may be a novel therapeutic target for neointimal formation.

Electroacupuncture Alleviates Pain Responses and Inflammation in Collagen-Induced Arthritis Rats via Suppressing the TLR2/4-MyD88-NF-κB Signaling Pathway.

Results: EA intervention and OxPAPC injection could relieve mechanical allodynia and thermal hyperalgesia caused by CIA. Paw edema and pathological damage of synovium were significantly ameliorated after EA intervention and OxPAPC injection. Furthermore, EA intervention and OxPAPC injection markedly reduced the contents of serum TNF-α, IL-1ß, and IL-6, as well as the protein expression levels of synovial TLR2, TLR4, MyD88, and NF-κB p-p65. In particular, the expression of TLR2 and TLR4 on synovial fibroblasts and macrophages in synovium was significantly reduced by EA intervention. Conclusions: Repeated EA stimulation at ST36 and SP6 can effectively relieve joint pain and synovial inflammation caused by RA in CIA rats. The analgesic and anti-inflammatory effect of EA may be closely related to the inhibition of innate immune responses driven by the TLR2/4-MyD88-NF-κB signaling pathway in the synovium.

Application of New Energy Thermochromic Composite Thermosensitive Materials of Smart Windows in Recent Years.

Thermochromic smart windows technology can intelligently regulate indoor solar radiation by changing indoor light transmittance in response to thermal stimulation, thus reducing energy consumption of the building. In recent years, with the development of new energy-saving materials and the combination with practical technology, energy-saving smart windows technology has received more and more attention from scientific research. Based on the summary of thermochromic smart windows by Yi Long research groups, this review described the applications of thermal responsive organic materials in smart windows, including poly(N-isopropylacrylamide) (PNIPAm) hydrogels, hydroxypropyl cellulose (HPC) hydrogels, ionic liquids and liquid crystals. Besides, the mechanism of various organic materials and the properties of functional materials were also introduced. Finally, opportunities and challenges relating to thermochromic smart windows and prospects for future development are discussed.

[Effects of transcutaneous auricular vagus nerve stimulation on bone and cartilage destruction in rats with rheumatoid arthritis].

OBJECTIVE: To observe the alleviating effect of transcutaneous auricular vagus nerve stimulation (taVNS) on articular cartilage and bone destruction in rats with collagen-induced arthritis (CIA), and explore the cellular and molecular mechanisms of taVNS against rheumatoid arthritis (RA). METHODS: The male SD rats were randomly divided into normal control group (n=12), model group (n=12), and taVNS group (n=12). The CIA rat model was established by multi-point injection of emulsion prepared from type Ⅱ bovine collagen and Freund's incomplete adjuvant into the root of rat tail. The rats in the taVNS group were treated with taVNS at bilateral auricular conchae, 30 min per time, once a day, for consecutive 28 d. The cartilage destruction of the ankle joint was observed by safranin O-fast green staining, the production of osteoclasts in the joint tissue by tartrate-resistant acid phosphatase (TRAP) staining, and the bone erosion by X-ray and Micro-CT imaging. The protein expression levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG) in the synovial tissues were detected by Western blot. RESULTS: Compared with the normal control group, the CIA rats presented with typical RA symptoms and elevated arthritis index (AI,P<0.05). After intervention with taVNS, the AI remarkably declined in comparison with that in the model group (P<0.05). Compared with the control group, the model group displayed loss of cartilage matrix in the ankle joint, thinned cartilage layer, obvious cartilage damage, and increased number of osteo-clasts in the joint (P<0.01); the imaging results showed bone loss and three-dimensional structural destruction of ankle joint and aggravated bone erosion (P<0.01); the expression levels of MMP-1, MMP-3 and MMP-13, and RANKL/OPG ratio were significantly elevated in the synovial tissue of ankle joint (P<0.01, P<0.05), while the expression level of OPG was decreased (P<0.05). Compared with the model group, taVNS resulted in relatively intact cartilage layer of ankle joint, alleviated cartilage destruction, decreased number of osteoclasts (P<0.01), improved bone erosion, loss, and three-dimensional structural destruction (P<0.01), and diminished MMP-1, MMP-3, and MMP-13 expression and RANKL/OPG ratio in the synovial tissue of ankle joint (P<0.05, P<0.01), while the expression level of OPG was increased (P<0.05). CONCLUSION: taVNS effectively relieves bone and cartilage destruction in CIA rats, which might be related to its efficacy in reducing the production of osteoclasts in joint tissues and down-regulating the expression levels of MMP-1, MMP-3 and MMP-13, and RANKL/OPG ratio.

RIP2 Knockdown Attenuates Vascular Smooth Muscle Cells Activation via Negative Regulating Myocardin Expression.

BACKGROUND: RIP2 is an adaptor protein contributing to the activation of nuclear factor-κB induced by TNF receptor-associated factor (TRAF) and nucleotide oligomerization domain (NOD)-dependent signaling implicated in innate and adaptive immune response. Beyond regulation of immunity, we aimed to elucidate the role of RIP2 in vascular smooth muscle cell (VSMC) phenotypic modulation. METHODS AND RESULTS: In the current study, we observed that RIP2 showed an increased expression in VSMCs with PDGF-BB stimulation in a dose-dependent manner. Knockdown of RIP2 expression mediated by adenovirus dramatically accelerated the expression of VSMC-specific differentiation genes induced by PDGF-BB. Silencing of RIP2 inhibited proliferative and migratory ability of VSMCs. Additionally, we demonstrated that RIP2 knockdown can promoted myocardin expression. Furthermore, RIP2 inhibition also can attenuate the formation of intimal hyperplasia. CONCLUSIONS: These findings suggested that RIP2 played an important role in regulation of VSMCs differentiation, migration, and proliferation that may due to affect myocardin expression. Our results indicated that RIP2 may be a novel therapeutic target for intimal hyperplasia.

MicroRNA-183 as a Novel Regulator Protects Against Cardiomyocytes Hypertrophy via Targeting TIAM1.

BACKGROUND: MicroRNAs serve as important regulators of the pathogenesis of cardiac hypertrophy. Among them, miR-183 is well documented as a novel tumor suppressor in previous studies, whereas it exhibits a downregulated expression in cardiac hypertrophy recently. The present study was aimed to examine the effect of miR-183 on cardiomyocytes hypertrophy. METHODS: Angiotensin II (Ang II) was used for establishment of cardiac hypertrophy model in vitro. Neonatal rat ventricular cardiomyocytes transfected with miR-183 mimic or negative control were further utilized for the phenotype analysis. Moreover, the bioinformatics analysis and luciferase reporter assays were used for exploring the potential target of miR-183 in cardiomyocytes. RESULTS: We observed a significant decreased expression of miR-183 in hypertrophic cardiomyocytes. Overexpression of miR-183 significantly attenuated the cardiomyocytes size morphologically and prohypertrophic genes expression. Moreover, we demonstrated that TIAM1 was a direct target gene of miR-183 verified by bioinformatics analysis and luciferase reporter assays, which showed a decreased mRNA and protein expression in the cardiomyocytes transfected with miR-183 upon Ang II stimulation. Additionally, the downregulated TIAM1 expression was required for the attenuated effect of miR-183 on cardiomyocytes hypertrophy. CONCLUSIONS: Taken together, these evidences indicated that miR-183 acted as a cardioprotective regulator for the development of cardiomyocytes hypertrophy via directly regulation of TIAM1.

Metal-free catalysis for the reaction of nitrogen dioxide dimer with phenol: An unexpected favorable source of nitrate and aerosol precursors in vehicle exhaust.

Atmospheric reaction mechanism and dynamics of phenol with nitrogen dioxide dimer were explored by the density functional theory and high-level quantum chemistry combined with statistical kinetic calculations within 220-800 K. The nitric acid and phenyl nitrite, the typical aerosol precursors, are the preponderant products because of the low formation free energy barrier (∼8.7 kcal/mol) and fast rate constants (∼10-15 cm3 molecule-1 s-1 at 298 K). Phenyl nitrate is the minor product and it would be also formed from the transformation of phenyl nitrite in NO2-rich environment. More importantly, kinetic effects and catalytic mechanism of a series of metal-free catalysts (H2O, NH3, CH3NH2, CH3NHCH3, HCOOH, and CH3COOH) on the title reaction were investigated at the same level. The results indicate that CH3NH2 and CH3NHCH3 can not only catalyze the title reaction by lowering the free energy barrier (about 1.4-6.5 kcal/mol) but also facilitate the production of organic ammonium nitrate via acting as a donor-acceptor of hydrogen. Conversely, the other species are non-catalytic upon the title reaction. The stabilization energies and donor-acceptor interactions in alkali-catalyzed product complexes were explored, which can provide new insights to the properties of aerosol precursors. Moreover, the lifetime of phenol determined by nitrogen dioxide dimer in the presence of dimethylamine may compete with that of determined by OH radicals, indicating that nitrogen dioxide dimer is responsible for the elimination of phenol in the polluted atmosphere. This work could help us thoroughly understand the removal of nitrogen oxides and phenol as well as new aerosol precursor aggregation in vehicle exhaust.

Effects of intracavitary administration of elemene combined with nedaplatin on malignant pleural effusion.

AIM: To investigate the therapeutic effect of Elemene combined with Nedaplatin (ECN) on malignant pleural effusion (MPE) and its adverse reactions. METHOD: A retrospective study was conducted, three hundred and fifty-two patients with MPE were divided into two groups according to different treatment methods. One hundred and eighty-nine patients were given intrathoracic injection of ECN and classified in ECN group; one hundred and sixty-three cases in the Nedaplatin group were given intrathoracic injection of nedaplatin. Routine treatments were used to prevent adverse reactions. RESULT: The effective rate of the ECN group was 57.05%, and that of the Nedaplatin group was 23.08%. The comparison results of adverse reactions between the two groups showed that there was no significant difference in leukopenia, thrombopenia, anemia, vomitting and diarrhea, fever, hepatic damage and renal damage. The level of thoracalgia in the ECN group was higher than that in the Nedaplatin group. There was no significant change in the number of CD8+ T cells between the two groups after treatment. The number of CD4+T cells in the ECN group increased after treatment was higher than the Nedaplatin group after treatment. CONCLUSION: ECN treatment can improve clinical control of MPE with no serious adverse reaction, can effectively reduce the immunosuppressive effect of nedaplatin and enhance the immune function of MPE patients which is worthy of clinical application.

The anti-neoplastic activities of aloperine in HeLa cervical cancer cells are associated with inhibition of the IL-6-JAK1-STAT3 feedback loop.

Cervical cancer (CC) is recognized as the most common neoplasm in the female reproductive system worldwide. The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients. Aloperine (ALO) is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation, allergies and infection. However, its therapeutic efficacy and underlying mechanism in CC are still unclear. In the current study, MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC. Then, the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry, respectively, while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay. Moreover, nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo. The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis. This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest. Simultaneously, ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio. Additionally, the migration and invasion of HeLa cells were attenuated by ALO treatment, which was considered to result from inhibition of epithelial-to-mesenchymal transition. For molecular mechanisms, the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment. This study indicated that ALO markedly suppresses the proliferation, migration and invasion and enhances the apoptosis of HeLa cells. In addition, these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.

[Effect of electroacupuncture on articular morphological changes and serum inflammatory factors and synovial MMPs in collagen-induced arthritis rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli"(ST36) and "Sanyinjiao"(SP6) on serum TNF-α, IL-1ß, and IL-6 and expression of synovial matrimetalloproteinases (MMPs) and articular morphology in collagen-induced arthritis (CIA) rats, so as to explore its mechanisms underlying relief of arthritis. METHODS: Thirty male SD rats were randomly divided into normal control, CIA model and EA groups (n=10 rats per group). The arthritis model was induced by multi-point intradermal injection of bovine type Ⅱ collagen emulsion. EA (2 Hz/100 Hz, 1 mA) was applied to bilateral ST36 and SP6 for 30 min, once a day for 28 days. The hind-limb paw volume was measured and the arthritis index (AI) score given according to the swelling degree, rigidity and deformity of the ankle joint (0-4 points). After EA intervention, the morphological damage of the affected ankle joints was revealed by H.E. staining, safranin O-fast green staining, and tartrate-resistant acid phosphatase (TRAP) staining, separately. The levels of serum TNF-α, IL-1ß, and IL-6 were measured by ELISA, and the expression levels of MMP-1, MMP-3, MMP-13, and receptor activator of nuclear factor Kappa B ligand (RANKL) in the synovial tissue were detected by Western blot. RESULTS: Compared with the normal control group, the paw volume, AI score, TRAP-revealed number of osteoclasts, contents of serum TNF-α, IL-1ß and IL-6, and expression levels of MMP-1, MMP-3, MMP-13 and RANKL proteins were significantly increased in the model group (P<0.01, P<0.05). Following the intervention, the paw volume, AI score, number of osteoclasts, contents of serum TNF- α, IL-1ß and IL-6, and expression levels of MMP-1, MMP-3, MMP-13 and RANKL proteins were significantly decreased in the EA group (P<0.05, P<0.01) in contrast to the model group. H.E. and safranin O-fast green staining showed rough articular cartilage surface with thinned cartilage layer, obvious hyperplasia of the synovial tissue with many inflammatory cells, and serious damage and degradation of the cartilage matrix in the model group, these situations were relatively milder in the EA group. CONCLUSION: EA of ST36 and SP6 can reduce the articular damage in collagen-induced arthritis rats, which is associated with its function in reducing inflammatory response and down-regulating the expression of synovial MMP-1, MMP-3, MMP-13 and RANKL proteins.

Attenuated macrophage activation mediated by microRNA-183 knockdown through targeting NR4A2.

Atherosclerosis is considered a chronic inflammatory disease, and macrophages function as important mediators in the development of atherogenesis. MicroRNA (miR)-183 is a small non-coding RNA that acts as a novel tumor suppressor and has recently been proposed to affect cardiac hypertrophy. However, the exact role and underlying mechanism of miR-183 in macrophage activation remain unknown. In the present study, miR-183 showed upregulated expression in atheromatous plaques and in bone marrow-derived macrophages (BMDMs) subjected to stimulation with oxidized low-density lipoproteins. Using a miR-183 loss-of-function strategy, it was demonstrated that miR-183 knockdown significantly increased resolving M2 macrophage marker expression but decreased proinflammatory M1 macrophage marker expression, as well as attenuated NF-κB activation. Moreover, decreased foam-cell formation accompanied by upregulation of genes involved in cholesterol efflux and downregulation of genes implicated in cholesterol influx was found in BMDMs transfected with a miR-183 inhibitor. Mechanistically, macrophage activation mediated by miR-183 silencing was partially attributed to direct upregulation of NR4A2 expression in BMDMs. Thus, the present study suggests that neutralizing miR-183 may be a potential therapeutic strategy for the treatment of atherosclerosis.

Elucidating the immune infiltration in acne and its comparison with rosacea by integrated bioinformatics analysis.

BACKGROUND: Acne vulgaris and rosacea are common inflammatory complications of the skin, both characterized by abnormal infiltration of immune cells. The two diseases can be differentiated based on characteristic profile of the immune cell infiltrates at the periphery of disease lesions. In addition, dysregulated infiltration of immune cells not only occur in the acne lesions but also in non-lesional areas of patients with the disease, thus characterizing the immune infiltration in these sites can further enhance our understanding on the pathogenesis of acne. METHODS: Five microarray data-sets (GSE108110, GSE53795, GSE65914, GSE14905 and GSE78097) were downloaded from Gene Expression Omnibus. After removing the batch effects and normalizing the data, we applied the CIBERSORT algorithm combined with signature matrix LM22, to describe 22 types of immune cells' infiltration in acne less than 48 hour (H) old, in comparation with non-lesional skin of acne patients, healthy skin and rosacea (including erythematotelangiectatic rosacea, papulopustular rosacea and phymatous rosacea) and we compared gene expression of Th1 and Th17-related molecules in acne, rosacea and healthy control. RESULTS: Compared with the non-lesional skin of acne patients, healthy individuals and rosacea patients, there is a significant increase in infiltration of neutrophils, monocytes and activated mast cells around the acne lesions, less than 48 H after their development. Contrarily, few naive CD4+ T cells, plasma cells, memory B cells and resting mast cells infiltrate acne sites compared to the aforementioned groups of individuals. Moreover, the infiltration of Regulatory T cells (Tregs) in acne lesions is substantially lower, relative to non-lesional sites of acne patients and skin of healthy individuals. In addition, non-lesional sites of acne patients exhibit lower infiltration of activated memory CD4+ T cells, plasma cells, memory B cells, M0 macrophages, neutrophils, resting mast cells but higher infiltration of Tregs and resting dendritic cells relative to skin of healthy individuals. Intriguingly, we found that among the 3 rosacea subtypes, the immune infiltration profile of papulopustular rosacea is the closest to that of acne lesions. In addition, through gene expression analysis of acne, rosacea and skin tissues of healthy individuals, we found a higher infiltration of Th1 and Th17 cells in acne lesions, relative to non-lesional skin areas of acne patients. CONCLUSIONS: Our study provides new insights into the inflammatory pathogenesis of acne, and the difference between acne and rosacea, which helps in differentiating the two diseases. Our findings also guide on appropriate target therapy of the immune cell infiltrates in the two disease conditions.

Intravenous Immunoglobulin Combined With Corticosteroids for the Treatment of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A Propensity-Matched Retrospective Study in China.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening severe adverse drug reactions. The use of corticosteroids and intravenous immunoglobulin (IVIg) in SJS/TEN remains controversial. Methods: In this single-center, observational, propensity-matched, retrospective study, we collected a total of 224 patients with SJS/TEN who were hospitalized in our department from 2008 to 2019; according to treatment with IVIg combined with corticosteroids or with corticosteroids alone, patients were divided into combination therapeutic group (163 patients) and monotherapeutic group (61 patients). Patients from the two groups were matched by their propensity score in blocks of 2:1. Comparisons of the clinical characteristics and prognoses between propensity-matched SJS/TEN patients treated with IVIg combined with corticosteroids and corticosteroids alone were made. Results: After our propensity matching, a total of 145 patients were yielded, including 93 patients treated with IVIg and 52 patients not treated with IVIg. All of the 23 variables reflected good matching between patients treated with/without IVIg, and no significant difference was observed. Although there was no significant difference between the totally predicted and actual mortality in both of our groups, the actual mortality was lower than it was predicted in patients treated with IVIg [p > 0.250, the standardized mortality ratio (SMR) was 0.38, 95% CI 0.00-0.91] and patients treated without IVIg (p = 1.000, the SMR was 0.75, 95% CI 0.00-1.76). IVIg tended toward reducing the time to arrest of progression by 1.56 days (p = 0.000) and the length of hospital stay by 3.37 days (p = 0.000). The mortality rate was 45% lower for patients treated with IVIg combined with corticosteroids than those only treated with corticosteroid therapy, although it was not statistically significant (p = 0.555). The incidence of skin infections was significantly lower in the combined therapy group (p < 0.025), and the total infection rate of patients treated with combination therapy tended to decrease by 67% compared to patients treated with corticosteroids alone (p = 0.047). Conclusion: The actual mortality rate of patients treated with corticosteroids alone or IVIg combined with corticosteroids tended to be lower than those predicted by TEN-specific severity-of-illness score (SCORTEN), although there was no significance. Compared with those treated by corticosteroids alone, combination therapy was prone to bring a better prognosis for SJS/TEN patients.

Synthesis, Crystal Structures and Luminescence Properties of Three New Cadmium 3D Coordination Polymers.

: The new rigid planar ligand 2,5-bis(3-(pyridine-4-yl)phenyl)thiazolo[5,4-d]thiazole (BPPT) has been synthesized, which is an excellent building block for assembling coordination polymer. Under solvothermal reaction conditions, cadmium ion with BPPT in the presence of various carboxylic acids including (1,1'-biphenyl)-4,4'-dicarboxylic acid (BPDC), isophthalic acid (IP), and benzene-1,3,5-tricarboxylic acid (BTC) gave rise to three coordination complexes, viz, [Cd(BPPT)(BPDA)](BPPT)n (1), [Cd(BPPT) (IP)] (CH3OH) (2), and [Cd3(BPPT)3(BTC)2(H2O)2] (3). The structures of 1, 2, and 3 were characterized by single crystal X-ray diffraction. The IR spectra as well as thermogravimetric and luminescence properties were also investigated. Complex 1 is a two-dimensional (2D) network and further stretched to a 3D supramolecular structure through π-π stacking interaction. The complexes 2 and 3 show 3D framework. The complexes 1, 2, and 3 exhibited luminescence property at room temperature.

Retrospective study of 213 cases of Stevens-Johnson syndrome and toxic epidermal necrolysis from China.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe adverse drug reactions with high mortality. The use of corticosteroids and the management of complications (e.g. infection) in SJS/TEN remains controversial. METHODS: A retrospective study was performed among 213 patients with SJS/TEN who were hospitalized in our department between 2008 and 2018, to investigate the causative agents, clinical characteristics, complications, and prognoses of SJS/TEN mainly treated by systemic corticosteroids combined with intravenous immunoglobulin (IVIG). RESULTS: The causative drugs of SJS/TEN in these patients mainly consisted of antibiotics (61/213, 28.6%), anticonvulsants (52/213, 24.4%), and nonsteroidal anti-inflammation drugs (24/213, 11.3%), among which carbamazepine was the most frequently administered drug (39/213, 18.3%). There were significant differences in the maximum dosage, time to corticosteroid tapering, and the total dosage of corticosteroid between the SJS group and the TEN group, as well as among the three groups (P = 0.000), whereas in the initial dose of corticosteroid was not statistically significant among the three groups (P = 0.277). In a series of 213 cases, 18.4 cases (8.6%) were expected to die based on the score for the toxic epidermal necrolysis (SCORTEN) system, whereas eight deaths (3.8%) were observed; the difference was not statistically significant (P = 0.067; SMR = 0.43, 95% CI: 0.06, 0.48). The most common complications were electrolyte disturbance (174/213, 81.7%), drug-induced liver injury (64/213, 30.0%), infection (53/213, 24.9%), and fasting blood sugar above 10 mmol/L (33/213, 15.5%). Respiratory system (22/213, 10.3%) and wound (11/213, 5.2%) were the most common sites of infection. Multivariate logistic regression analysis indicated that the maximum blood sugar (≥10 mmol/L), the time to corticosteroid tapering (≥12 d), the maximum dosage of corticosteroid (≥1.5 mg/kg/d), and the total body surface area (TBSA) (≥10%) were defined as the most relevant factors of the infection. CONCLUSION: The mortality of patients in this study was lower than that predicted by SCORTEN, although there was no significant difference between them. Hyperglycemia, high-dose corticosteroid, and the TBSA were closely related to the infections of patients with SJS/TEN.

ACUTE MACULAR NEURORETINOPATHY IN SUSAC SYNDROME: A NEW ASSOCIATION.

PURPOSE: To report a case of acute macular neuroretinopathy in a patient with Susac syndrome. METHODS: Case report. RESULTS: A 39-year-old male patient presented with severe headache, photopsias, and a sudden onset of hearing loss in the right ear. Fluorescein angiography of the right eye revealed multiple branch retinal artery occlusions. Clinical presentation of encephalopathy, hearing loss, and branch retinal artery occlusions, along with characteristic magnetic resonance imaging findings, led to a diagnosis of Susac syndrome. Despite aggressive immunosuppression for four months, the patient later presented with acute macular neuroretinopathy in the left eye. CONCLUSION: Acute macular neuroretinopathy and Susac is a new association of two well-defined disorders. The concurrence of both disorders supports retinal ischemia as the proximate cause of acute macular neuroretinopathy and inflammation as a potential etiology.

[Changes of soil enzyme activities and nutrients across different succession stages of grazing alpine Kobresia grassland.] / æ”¾ç‰§é«˜å¯’åµ©è‰è‰åœ°ä¸åŒæ¼”æ›¿é˜¶æ®µåœŸå£¤é ¶æ´»æ€§åŠå »åˆ†æ¼”å˜ç‰¹å¾.

The variation of soil enzyme activity and relevance with soil nutrients was examined in multistable grazing alpine Kobresia grassland, including Gramineae-Kobresia humilis community, K. humilis community, K. pygmaea community at thickened stage, K. pygmaea community at cracked stage and forb-black soil type secondary bare land. The results showed that the vegetation coverage and aboveground biomass successively decreased with degenerative succession. The belowground biomass was the highest in the K. pygmaea community at thickened and cracked stages. The activities of soil sucrase, urease, cellulase, alkaline phosphatase and aryl sulfatase were higher at the surface soil layer (0-10 cm) than those at the subsurface soil layer (10-20 cm), while the pattern of chitinase activity was contrary. The activities of cellulase, alkaline phosphatase and aryl sulfatase were the highest in the Gramineae-K. humilis community and the lowest at the forb-black soil type secondary bare land, and they slightly increased during the thickened stage of K. pygmaea community. Chitinase activity was relatively high at the middle three stages, while urease and sucrase activity had an obvious increase in the forb-black soil type secondary bare land. Soil moisture, ammonium, alkali-hydrolyzable nitrogen, total nitrogen, total carbon and organic carbon successively decreased with degenerative succession, whereas the concentrations of nitrate and available phosphorus increased at the latter two succession stages. The activities of the other enzymes, except for chitinase, were significantly positively correlated with the soil available phosphorus, ammonium, alkali-hydrolyzed nitrogen, total carbon, and organic carbon, and negatively correlated with soil pH. The activities of cellulose, alkaline phosphatase and aryl sulfatase were significantly positively correlated with soil moisture and total nitrogen. The main factors affecting soil enzyme activity were available phosphorus and ammonium. Soil enzymes showed different evolutionary trends influenced by grazing degradation succession in the alpine grassland, with a synergistic effect with soil nut-rients. Moreover, severely degraded extreme environments may stimulate soil enzyme activities related to nitrogen and carbon transformation.

Contribution of GABAergic modulation in DRGs to electroacupuncture analgesia in incisional neck pain rats.

PURPOSE: Acupuncture therapy is effective for relieving postoperative pain. Our previous study showed that electroacupuncture (EA) at Futu (LI18) and Hegu (LI4)-Neiguan (PC6) could alleviate incisional neck pain, which was related with its effect in upregulating γ-aminobutyric acid (GABA) expression in cervical (C3-6) dorsal root ganglions (DRGs); but whether its receptor subsets GABAAα2R and GABABR1 in C3-6 DRGs are involved in EA analgesia or not, it remains unknown. MATERIALS AND METHODS: Seventy-five male Sprague Dawley rats were randomized to normal control, model, LI18, LI4-PC6, and Zusanli (ST36)-Yanglingquan (GB34) groups. The incisional neck pain model was established by making a longitudinal incision along the midline of the rats' neck, followed by repeated mechanical stimulation. EA was applied to bilateral LI18, LI4-PC6, or ST36-GB34 for 30 minutes at 4, 24, and 48 hours after operation. The thermal pain threshold of the neck was detected by a tail-flick unit, and the C3-6 DRGs were removed for assaying the immunoactivity of substance P (SP), GABAAα2R, glial fibrillary acidic protein (GFAP; a marker of satellite glial cells [SGCs]), and GABABR1 and the expression of GABAAα2R and GABABR1 mRNA and proteins using immunofluorescence, real-time PCR, and Western blotting, respectively. RESULTS: The cervical thermal pain threshold was significantly lower in the model group than the normal group (P<0.001), indicating hyperalgesia after neck incision, and was considerably increased in both EA-LI18 and LI4-PC6 groups (P<0.001), but not in ST36-GB34 group compared with model group (P>0.05). Immunofluorescence staining showed that GABAAα2 R expressed on SP+ neurons, and GABABR1 on SGCs. EA of LI18 and LI4-PC6 markedly suppressed the modeling-induced upregulation of the immunoactivity of SP (P<0.001 and P<0.01, respectively) and GFAP (P<0.01 and P<0.001, respectively) and significantly reversed neck incision-induced downregulation of the expression of GABAAα2R and GABABR1 mRNAs and proteins (P<0.05). CONCLUSION: EA of LI18 and LI4-PC6 has an analgesic effect in incisional neck pain rats, which is related to its effects in upregulating GABAergic inhibitory modulation on nociceptive peptidergic neurons and SGCs in cervical DRGs.

Association Between Unstable Angina and CXCL17: a New Potential Biomarker.

Atherosclerosis and chemokines are strongly related, but the role of the chemokine CXCL17 in atherogenesis is still poorly understood. We aim to investigate the serum CXCL17 levels in different stages of patients with coronary heart disease and explore whether these differences contribute to atherosclerosis. In the current prospective study, we enrolled 48 patients with unstable angina (UA), 51 patients with stable angina (SA) and 41 patients for the control group (CG). All subjects were diagnosed by coronary angiography and Gensini score was used to evaluate the severity of coronary artery disease. The CXCL17 levels were determined using ELISA, while lipid metabolism indicators and high sensitivity C-reactive protein (hs-CRP) were detected by automatic biochemical analyzer. We observed that the unstable angina group had higher CXCL17 levels compared with the stable angina and the control group. The logistic regression analysis showed that CXCL17 was an independent risk factor for unstable angina. Our results showed that CXCL17 was also statistically correlated with hs-CRP, while it was irrelevant with Gensini score. CXCL17 levels were associated with activity of inflammatory response and the instability of atherosclerotic plaques. These results suggest that CXCL17 elevation may be a potential new biomarker of unstable angina.