Objective To investigate the influence of volatile oil from Acori graminei Rhizoma (VOA) on expressions of glial fibrillary acidic protein (GFAP), c-Jun N-terminal protein kainse (JNK) and tumour necrosis factor-α (TNF-α) in the spinal cord dorsal horn of imflammatory pain rats. Methods Totally 36 male SD rats were randomly divided into control group (control), sham-operated group (sham), complete Freund' s adjuvant group (CFA), 5 g/(kg·d) low dose VOA+CFA group (VOA-L+CFA), 10 g/(kg·d) medium dose VOA + CFA group (VOA-M+CFA) and 20 g/(kg·d) high dose VOA + CFA group (VOA-H+CFA). All animals were sacrificed immediately after continuous gavage administration for 22 days. The expressions of GFAP, JNK and TNF-α in the spinal cord dorsal horn of rats in each group were detected by immunofluorescence and Western blotting methods. Results The present results showed that the positive expressions of GFAP, JNK and TNF-α in the spinal cord dorsal horn of rats increased significantly in the CFA group, when compared to the control and sham groups (P < 0. 01). The expressions of GFAP, JNK and TNF-α in the spinal cord dorsal horn of rats with VOA treatment reduced in the dose-dependent manner, when compared to the CFA group, the positive expressions of GFAP, JNK and TNF-α reduced significantly in the dorsal horn of the spinal cord of the VOA-H+CFA group (P<0. 05, P<0. 01). Conclusion VOA reduces the expressions of GFAP, JNK and TNF-α in the spinal cord dorsal horn of rats of CFA-induced inflammatory pain.

Background Under the background of global climate change, temperature has increased dramatically. Most studies about association between temperature and human health are conducted in low-altitude areas, but rarely focus on plateau areas. Objective To examine the association between temperature and non-accidental mortality risk in Tibet Plateau, China and to identify vulnerable populations for formulating targeted policies of climate change adaptation. Methods The mortality data, meteorological data, and pollutant data of Tibet area between 2013 to 2019 were collected. Based on time-stratified case-crossover design, conditional logistic regression models were used to analyze the exposure-response relationship between temperature and cause-specific mortality, which was linearized to obtain excess risk for 1 ℃ change; attributable fraction was calculated for assessing burden attributable to temperature; and stratified analyses were further conducted by gender, age (＜65 years old, ≥65 years old), and causes of death (cardiovascular diseases, cerebrovascular diseases, and respiratory diseases). Sensitivity analyses were conducted by adjusting model parameters and variables. Results A total of 26 045 non-accidental deaths were collected in Tibet during 2013 and 2019, and the P₅₀ of temperature was 5.0 ℃. The non-accidental mortality risk increased as temperature become colder. A 1 ℃ decrease in temperature was associated with a 2.01% (95%CI: 0.94%-3.07%) increase in total non-accidental mortality, while the association changed to 2.05% (95%CI: 0.62%-3.47%) for male and 1.96% (95%CI: 0.34%-3.56%) for female, both of statistial significance; 1.45% (95%CI: −0.10%-2.98%) for the people <65 years old (not of significance) and 2.52% (95% CI : 1.04%-3.99%) for the people ≥65 years old (of significance); the excess risk for cardiovascular mortality was 2.65% (95%CI: 1.03%-4.24%), for cerebrovascular mortality was 3.70% (95%CI: 0.74%-6.57%), both of statistical significance, and for respiratory mortality was 2.18% (95%CI: −0.14%-4.44%), without significance. The total attribution number of non-accidental mortality was 5340 (95%CI: 2719-7528), and the total attributable fraction was 20.50% (95%CI: 10.44%-28.91%). The attributable fractions were higher in specific subgroups like male (20.72%), people ≥65 years (23.33%), and people with cardiovascular diseases (26.07%). Conclusion The exposure-response relationship between temperature and non-accidental mortality in Tibet showes that the non-accidental mortality risk increase as temperature become colder. The attributable burden of disease is heavy. Residents being male, ≥65 years, with cardiovascular diseases and respiratory diseases may be vulnerable to nonoptimal temperature.

Gadoxetate magnetic resonance imaging (MRI) is widely used in clinical practice for liver imaging. For optimal use, we must understand both its advantages and limitations. This article is the outcome of an online advisory board meeting and subsequent discussions by a multidisciplinary group of experts on liver diseases across the Asia-Pacific region, first held on September 28, 2020. Here, we review the technical considerations for the use of gadoxetate, its current role in the management of patients with hepatocellular carcinoma (HCC), and its relevance in consensus guidelines for HCC imaging diagnosis. In the latter part of this review, we examine recent evidence evaluating the impact of gadoxetate on clinical outcomes on a continuum from diagnosis to treatment decision-making and follow-up. In conclusion, we outline the potential future roles of gadoxetate MRI based on an evolving understanding of the clinical utility of this contrast agent in the management of patients at risk of, or with, HCC.

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CL^pro) and papain-like protease (PL^pro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CL^pro and PL^pro with IC₅₀ values of 1.73 ± 0.22 and 3.91 ± 0.19 μmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC₅₀ of 11.83 ± 3.23 μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CL^pro, and K157, E167 and A246 of PL^pro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.

Objective: The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases. Methods: A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up. Results: Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases. Conclusions Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.
COVID-19/complications* ; Follow-Up Studies ; Humans ; Olfaction Disorders/etiology* ; Pandemics ; Prospective Studies ; SARS-CoV-2

OBJECTIVE: To analyze the relationship between cervical vertigo and vestibular function evaluated by vestibular evoked myogenic potentials(VEMPs) and analyze the correlations between cervical vertigo and vestibular dysfunction, discuss the related factors of cervical vertigo and guide the clinical treatment of patients with cervical vertigo. METHODS: A total of 75 patients with cervical vertigo as the main complaint in the outpatient clinic of the Second Hospital of Shanxi Medical University from August 2019 to July 2020 were set as the diseased group, and 60 patients without cervical and vestibular related diseases in the hospital were selected to set as non-diseased group. The age of diseased group was 12 to 70 years with an average of (46.40±10.91) years, including 25 males and 50 females;and the age of non-diseased group was 22 to 60 years with an average of(43.78±7.75) years, including 19 males and 51 females. VEMPs were performed in the two groups. The data of VEMPs were collected and the results were compared and analyzed. The patients with abnormal cervical myogenic vestibular evoked myogenic potential (cVEMP) were divided into light, moderate and severe groups. The correlation between VEMPs and cervical vertigo and its severity were analyzed by statistical method. RESULTS: (1)The severity of cervical vertigo in diseased group:33 cases of mild, 34 cases of moderate, 8 cases of severe; cVEMP examination:62 cases were positive and 13 cases were negative, including 13 cases of mild, 33 cases of moderate, 16 cases of severe. The cVEMP of non-diseased group:4 cases were positive and 56 cases were negative.(2) The level of cVEMP in diseased group was higher than that in non-diseased group (P<0.001). It can be considered that there was a correlation between cervical vertigo and vestibular function.(3)The correlation between the level of cVEMP and the level of cervical vertigo in diseased group was analyzed. The Spearman rank sum test was used, and the correlation coefficient was 0.687, which was statistically significant (P<0.05). And it can be considered that the two indicators have a high degree of correlation. CONCLUSION It is feasible to evaluate the relationship between cervical vertigo and vestibular function by VEMPs. For patients with cervical vertigo, the higher the severity, the greater the positive rate of VEMPs, which indicates that it has a greater impact on vestibular function. The treatment of patients with cervical vertigo should be the combination of cervical rehabilitation and vestibular function.
Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Male ; Middle Aged ; Neck ; Vertigo ; Vestibular Evoked Myogenic Potentials/physiology* ; Young Adult

Objective: To investigate the clinicopathological features, molecular characteristics, differential diagnosis and prognosis of anaplastic lymphoma kinase (ALK)-translocation renal cell carcinoma. Methods: Two cases of ALK-translocation renal cell carcinoma diagnosed from January 2011 to December 2020 were retrospectively analyzed to characterize their morphological features, immunohistochemical expression and prognosis. Multiple molecular studies including fluorescence in situ hybridization (FISH), reverse transcriptase-polymerase chain reaction (RT-PCR), and next-generation sequencing were performed to characterize the genetic alterations. Results: Two patients included one male and one female, with 59 and 57 years old, respectively. Morphologically, case 1 resembled collecting duct carcinoma or renal medullary carcinoma, which demonstrated tubular, microcapsule and reticular structures, with a remarkable myxoid background and lymphocytes infiltration; case 2 resembled Xp11.2 translocation renal cell carcinoma or type 2 papillary renal cell carcinoma, which demonstrated tubular papillary and focal solid structures, with flocculent cytoplasm and many foamy histiocytes, but without myxoid background and lymphocytes infiltration. Immunohistochemistry showed strongly positive expression of ALK. CK7, E-cadherin, vimentin, PAX8 and CD10 showed various degrees of expression, and other antibodies were nonreactive. A variety of molecular assays showed definite ALK gene translocation, with rare VCL-ALK gene fusion (VCL exon and 16-ALK exon 20) in case 1, and EML4-ALK gene fusion (EML4 exon and 2-ALK exon 20) in case 2. Conclusions: ALK-translocation renal cell carcinoma is rare with various morphological features, and is easy to miss and misdiagnose. The characteristic ALK expression and molecular detection of ALK translocation are helpful for diagnosing this type of renal cell carcinoma.
Anaplastic Lymphoma Kinase/genetics* ; Carcinoma, Renal Cell/genetics* ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Kidney Neoplasms/genetics* ; Lung Neoplasms ; Male ; Oncogene Proteins, Fusion/genetics* ; Retrospective Studies

OBJECTIVE: To evaluate the protective effects of Astragaloside IV (AST) in a rat model of myocardial injury induced by cecal ligation and puncture (CLP). METHODS: The model of sepsis-induced cardiac dysfunction was induced by CLP. Using a random number table, 50 specific pathogen free grade of Sprague Dawley rats were randomized into 5 groups: the sham group (sham), the model group (CLP, 18 h/72 h) and AST group (18 h/72 h). Except the sham group, the rats in other groups received CLP surgery to induce sepsis. CLP groups received intragastric administration with normal saline after CLP. AST groups received intragastric administration with AST solution (40 mg/kg) once a day. The levels of inflammatory mediators and oxidative stress markers in the serum of the septic rats were determined via enzyme-linked immunosorbent assay (ELISA) at different time point, such as interleukin 6 (IL-6), IL-10, high mobility group box-1 protein B1 (HMGB-1), superoxide dismutase (SOD), and malondialdehyde (MDA). Cardiac function was determined by echocardiography. Moreover, changes in myocardial pathology were evaluated using hematoxylin and eosin staining. The levels of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were analysed to determine the status of CLP-induced myocardium. In addition, the apotosis of myocardial cells was analysed by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). The protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), IκB kinase α (IKKα), nuclear factor kappa B p65 (NF-κB p65) were detected by Western blot analysis. Moreover, survival rate was investigated. RESULTS: AST improved the survival rate of CLP-induced rats by up to 33.3% (P<0.05). The cardioprotective effect of AST was observed by increased ejection fraction, fractional shortening and left ventricular internal diameter in diastole respectively (P<0.01 or P<0.05). Subsequently, AST attenuated CLP-induced myocardial apoptosis and the ratio of Bcl-2/Bax in the myocardium, as well as the histological alterations of myocardium (P<0.01 or P<0.05); the generation of inflammatory cytokines (IL-6, IL-10, HMGB-1) and oxidative stress markers (SOD, MDA) in the serum was significantly alleviated (P<0.01 or P<0.05). On the other hand, AST markedly suppressed CLP-induced accumulation of IKK-α and NF-κB p65 subunit phosphorylation (P<0.01 or P<0.05). CONCLUSIONS AST plays a significant protective role in sepsis-induced cardiac dysfunction and survival outcome. The possible mechanism of cardioprotection is dependent on the activation of the IKK/NF-κB pathway in cardiomyocytes.
Animals ; Disease Models, Animal ; Heart Diseases ; NF-kappa B ; Rats ; Rats, Sprague-Dawley ; Saponins ; Sepsis/drug therapy* ; Triterpenes ; Tumor Necrosis Factor-alpha

Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation by activating nuclear factor-κB (NF-κB). Sirtuin 2 (SIRT2) is a key modulator in inflammation. However, the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied. Therefore, this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues. Subsequently, SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway. The activation of p65 triggered airway inflammation, increment of mucus secretion by goblet cells, and acceleration of tracheal stenosis. Meanwhile, p65 phosphorylation and acetylation, airway inflammation, and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5. Triptolide (a specific p65 inhibitor) reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure. Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.
Animals ; Inflammation ; Mice ; NF-kappa B/metabolism* ; Particulate Matter/toxicity* ; Signal Transduction ; Sirtuin 2/metabolism* ; Transcription Factor RelA/metabolism*