Clinical Use of Intravenous Fosfomycin in Critical Care Patients in Taiwan.

This retrospective study aimed to evaluate the clinical use and side effects of fosfomycin in critically ill patients in Taiwan. Forty-two patients (mean age, 69.9 years; female, 69%) who received fosfomycin were included from a teaching hospital in Taiwan from January 2021 to December 2021. We analyzed the prescription pattern of intravenous fosfomycin and evaluated patient safety profiles, clinical successes, and microbiological cure rates. The main indication was urinary tract infections (35.6%), and the most frequently identified pathogen was Escherichia coli (18.2%). The overall clinical success was 83.4%, with one multidrug-resistant pathogen isolated from eight patients (19.0%). The average dose of fosfomycin given was 11.1 ± 5.2 g/day. The average duration of therapy was 8.7 ± 5.9 days, with a median duration of 8 days, where fosfomycin was mostly (83.3%) given in combination. Fosfomycin was given 12 hourly to a maximum number (47.6%) of cases. The incidence rates of adverse drug reactions (hypernatremia and hypokalemia) were 33.33% (14/42) and 28.57% (12/42), respectively. The overall survival rate was 73.8%. Intravenous fosfomycin may be an effective and safe antibiotic to use in combination with other drugs for empirical broad-spectrum or highly suspected multidrug-resistant infections in critically ill patients.

Discovery of benzochalcone derivative as a potential antigastric cancer agent targeting signal transducer and activator of transcription 3 (STAT3).

Gastric cancer remains a significant health burden worldwide. In continuation of our previous study and development of effective small molecules against gastric cancer, a series of benzochalcone analogues involving heterocyclic molecules were synthesised and biologically evaluated in vitro and in vivo. Among them, the quinolin-6-yl substituted derivative KL-6 inhibited the growth of gastric cancer cells (HGC27, MKN28, AZ521, AGS, and MKN1) with a submicromolar to micromolar range of IC50, being the most potent one in this series. Additionally, KL-6 significantly inhibited the colony formation, migration and invasion, and effectively induced apoptosis of MKN1 cells in a concentration-dependent manner. The mechanistic study revealed that KL-6 could concentration-dependently suppress STAT3 phosphorylation, which may partly contribute to its anticancer activity. Furthermore, in vivo antitumour study on the MKN1 orthotopic tumour model showed that KL-6 effectively inhibited tumour growth (TGI of 78%) and metastasis without obvious toxicity. Collectively, compound KL-6 may support the further development of candidates for gastric cancer treatment.

Trametes robiniophila Murr Sensitizes Gastric Cancer Cells to 5-Fluorouracil by Modulating Tumor Microenvironment.

Trametes robiniophila Murr (TRM) is a traditional Chinese medicine which has been used in clinics for enhancing immunity and improving the efficacy of chemotherapy. However, the mechanisms of action of TRM are unknown. In the previous study, we found that the Trametes robiniophila Murr n-butanol extract (TRMBE) comprises the major bioactive components of TRM. In the present study, we aimed to assess the combinational effects of TRMBE and 5-fluorouracil (5-FU) on the treatment of gastric cancer (GC) and explore its mechanism of action. It was found that TRMBE significantly potentiated the anticancer activity of 5-FU and prolonged the survival time of mice bearing Mouse Forestomach Carcinoma (MFC) xenograft tumors. We observed that the combination of TRMBE and 5-FU decreased the risk of liver metastasis in vivo. Furthermore, the combination of TRMBE and 5-FU reduced the levels of immune cytokines IL-6, IL-10, and TGF-ß and increased the level of IFN-γ in peripheral blood. This combination therapy also significantly decreased the levels of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and PD-1-positive CD8+ T cells and increased the levels of NK cells in tumor microenvironment (TME). However, TRMBE treatment was unable to enhance the chemosensitivity of GC to 5-FU in vivo after the depletion of CD8+ T and NK cells. Taken together, our results demonstrate that TRMBE can reshape the TME of GC by regulating PMN-MDSCs, CD8+ T cells, and NK cells, therefore improving the therapeutic effects of 5-FU. This study suggests that the combination of TRMBE and 5-FU could enhance immunity and could be a promising approach for GC treatment.

Unilateral pulmonary oedema: a case report and literature review.

Acute myocarditis is often secondary to an acute virus infection, which can be the first manifestation of upper respiratory tract symptoms, followed by chest tightness, shortness of breath, palpitations, chest pain and other non-specific symptoms. In severe cases, it can quickly progress to serious complications such as heart failure, shock and respiratory failure. Laboratory examinations can show an increase of myocardial injury markers, infection and inflammatory indicators. Cardiac ultrasound can detect the weakening of the myocardial contraction and valve regurgitation. On imaging, bilateral pulmonary oedema demonstrates symmetrical infiltration along the hilum of lung, called the "butterfly shadow". This current case report describes a patient with unilateral pulmonary oedema caused by myocarditis that was initially misdiagnosed and treated as pneumonia. The patient was subsequently treated with the application of extracorporeal membrane oxygenation and he made a full recovery. A review of this case highlights that when a patient's symptoms are not typical, a comprehensive examination and evaluation are required to avoid incorrect treatment.

The value of SPECT/CT imaging of lacrimal glands as a means of assessing the activity of Graves' orbitopathy.

Background: Graves' orbitopathy (GO) is an autoimmune disease with mechanical impairment of orbital muscles and lacrimal gland dysfunction. The frequently used methods of assessing GO activity include Clinical Activity Score (CAS), CT, and MRI. These approaches are mainly associated with orbital muscles; however, there are not many studies that focus on the lacrimal gland inflammation of GO patients. Objective: The aim of this study is to assess the usefulness of 99mTc-DTPA single-photon emission (SPE) CT/CT in evaluating the lacrimal gland inflammation in GO, as compared with other methods. Methods: A retrospective analysis of 48 patients with active GO compared with 33 controls was conducted. All subjects underwent clinical-endocrinological analyses, CAS evaluation, CT scans, and SPECT/CT examination. Lacrimal gland dimensions were determined and analyzed. Results: The lacrimal glands in patients with GO were significantly larger in all measured dimensions (P < 0.001) on CT scans relative to those in controls. Increased lacrimal gland diethylene triamine pentaacetic acid (DTPA) uptake ratios (P < 0.001) were displayed in active GO patients compared to controls and were also correlated with thyrotropin receptor antibody levels. The cut-off value for discriminating active and inactive disease was calculated to be 1.735, with specificity of 82.6% and sensitivity of 74.2%. SPECT/CT uptake ratios and CAS values were positively correlated in all GO patients. SPECT/CT uptake ratios were also positively correlated with CT measurements including lacrimal gland volume and coronal width in GO patients. Conclusions: These data indicated that lacrimal gland SPECT/CT images can serve as a good tool for assessing the inflammation and disease activity of GO.

(±)-Involucrasins A and B, two pairs of flavanone enantiomers from Shuteria involucrata and their inhibitory effects on the proliferation of various cancer cell lines.

(±)-Involucrasins A (1) and B (2), two pairs of flavanone enantiomers were isolated from Shuteria involucrata. Structurally, both 1 and 2 are rare representatives of 5-dehydroxy/5-demethoxy 2',3',4'-trisubstituted flavanones. Their structures were elucidated on the basis of comprehensive spectroscopic data analysis and comparison with the literature data. Involucrasin B (2) exhibited moderate anti-proliferative activity against Caco-2, MCF-7, MDA-MB-468, and HCT116 cell lines with IC50 values ranging from 7.9-22.7 µM. Involucrasin A (1) exhibited weak inhibitory activity against Caco-2 and MCF-7 cell lines with IC50 values of 25.8 and 26.5 µM, respectively.

Antibody and complement levels in patients with hypersplenism associated with cirrhotic portal hypertension and therapeutic principles.

BACKGROUND: Hypersplenism associated with cirrhotic portal hypertension is a common condition often resulting from hepatitis B-related cirrhosis. However, the levels of immunoglobulin (Ig) and complement in patients with hypersplenism associated with cirrhotic portal hypertension remain unclear. This study was undertaken to determine the levels of Ig and complement in these patients, the relationship between these levels and Child-Pugh class and their clinical significance. AIM: To investigate the antibody (Ig) and complement levels in patients with hypersplenism associated with cirrhotic portal hypertension and their clinical significance. METHODS: Clinical data of 119 patients with hypersplenism associated with cirrhotic portal hypertension were statistically analyzed and compared with those of 128 control patients. RESULTS: IgA and IgG levels in patients with hypersplenism were significantly higher than controls (P < 0.001). There was no significant difference in IgM between the two groups (P = 0.109). C3 and C4 levels in patients with hypersplenism were significantly lower than controls (P < 0.001). As liver function decreased, IgA and IgG levels increased (P < 0.001), and C3 and C4 levels decreased (P < 0.001). CONCLUSION: Patients with hypersplenism associated with cirrhotic portal hypertension have significantly higher antibody (IgA and IgG) levels and significantly lower complement (C3 and C4) levels, which are both related to liver damage. Clinically, the administration of anti-hepatitis virus agents and protection of liver function should be strengthened.

Investigation on radon exposure level in 38 districts and counties in Chongqing / 中国热带医学

@#Abstract: Objective　In order to understand the radon exposure level of homes in Chongqing, this survey was carried out on the indoor radon concentration in 38 districts and counties of Chongqing. Methods　According to the population ratio of every 100 000 people, one monitoring site was arranged, and the number of parallel samples was 10% of the distribution sites. The monitoring sites covered 38 districts and counties in Chongqing. A total of 1 019 residential monitoring sites in 38 districts and counties in Chongqing were measured with radon accumulation detectors from July 2020 to June 2021. Results　The five districts/counties in Chongqing having the highest average concentration of residential radon in the year were Xiushan County 78.8 Bq/m3, Qianjiang District 78.0 Bq/m3, Yubei District 73.9 Bq/m3, Youyang County 71.4 Bq/m3 and Shapingba District 69.8 Bq/m3. The five districts/counties with the lowest mean concentration of indoor radon were 37.6 Bq/m3 in Zhongxian County, 36.4 Bq/m3 in Changshou District, 33.7 Bq/m3 in Kaizhou District, 33.2 Bq/m3 in Liangping District and 27.3 Bq/m3 in Wushan County. The concentration levels of radon in four seasons were 46.0 Bq/m3, 53.4 Bq/m3, 45.1 Bq/m3 and 59.5 Bq/m3, respectively. The concentration of radon was higher in Summer and Winter, and lower in Spring and Autumn, and the difference of concentration among four seasons was statistically significant (P<0.001). The radon concentration of newly built buildings after 2017 was relatively high, up to 61.8 Bq /m3, but there was no statistical significance in radon concentration in different building ages (P>0.05). The concentration of radon in rooms of buildings with less than 10 floors was higher, up to 63.2 Bq /m3, and there were significant differences in radon concentration among rooms of different floors (P<0.05). The average annual radon concentration in houses in Chongqing was about (51.6±19.5) Bq/m3, and the average annual effective dose of inhaling radon and its progeny by house-related people was about (1.38±0.52) mSv. Conclusion　The average annual radon concentration level of houses in Chongqing is within the standard limit value recommended by China, but the prevention and control of radon should be strengthened.

Mechanism study of rhubarb-peach kernel regulation of feces metabolic profile in mice with adenomyosis / 药学学报

This paper aims to investigate the regulatory mechanism of blood-activating and stasis-dissipating drugs on fecal metabolic characteristics of rhubarb-peach kernel in mice with adenomyosis (AM) using fecal metabolome method. Adenomyosis was modeled by pituitary transplantation, and after the end of modeling administration, fecal samples were collected from mice. Non-targeted metabolomics studies were performed using liquid chromatography-mass spectrometry (LC-MS) to compare the metabolic characteristics of the feces of mice in each group and to find intestinal differential metabolites and potential differential metabolic pathways. The results showed that compared with the normal group, 5-hydroxy-L-tryptophan, histidine, L-acetylcarnitine, 16-hydroxy hexadecanoic acid, thromboxane B2, etc. were significantly up-regulated, L-urobilin and prostaglandin D3 were down-regulated in the feces of the model group, and were reversed after treatment with the rhubarb-peach kernel. The results of metabolic pathway enrichment analysis showed that tryptophan metabolism and histidine metabolism were the main intervention pathways of the rhubarb-peach kernel on AM intestinal metabolism. This study found that the underlying mechanism of the rhubarb-peach kernel in the treatment of AM is related to the intervention of intestinal metabolism of tryptophan, histidine, bile acid, choline and arachidonic acid, and the regulation of pro-inflammatory microenvironment and fatty acid metabolic homeostasis. This study has been approved by the Experimental Animal Ethics Committee of China Three Gorges University (No. 20190801).

Species identification and phylogenetic analysis of Leishmania isolated from patients, vectors and hares in the Xinjiang Autonomous Region, The People's Republic of China.

BACKGROUND: Visceral leishmaniasis (VL) has been declared as one of the six major tropical diseases by the World Health Organization. This disease has been successfully controlled in China, except for some areas in the western region, such as the Xinjiang Autonomous Region, where both anthroponotic VL (AVL) and desert type zoonotic VL (DT-ZVL) remain endemic with sporadic epidemics. METHODOLOGY/PRINCIPAL FINDINGS: Here, an eleven-year survey (2004-2014) of Leishmania species, encompassing both VL types isolated from patients, sand-fly vectors and Tarim hares (Lepus yarkandensis) from the Xinjiang Autonomous Region was conducted, with a special emphasis on the hares as a potential reservoir animal for DT-ZVL. Key diagnostic genes, ITS1, hsp70 and nagt (encoding N-acetylglucosamine-1-phosphate transferase) were used for phylogenetic analyses, placing all Xinjiang isolates into one clade of the L. donovani complex. Unexpectedly, AVL isolates were found to be closely related to L. infantum, while DT-ZVL isolates were closer to L. donovani. Unrooted parsimony networks of haplotypes for these isolates also revealed their relationship. CONCLUSIONS/SIGNIFICANCE: The above analyses of the DT-ZVL isolates suggested their geographic isolation and independent evolution. The sequence identity of isolates from patients, vectors and the Tarim hares in a single DT-ZVL site provides strong evidence in support of this species as an animal reservoir.

Innate Resistance to Leishmania amazonensis Infection in Rat Is Dependent on NOS2.

Leishmania infection causes diverse clinical manifestations in humans. The disease outcome is complicated by the combination of many host and parasite factors. Inbred mouse strains vary in resistance to Leishmania major but are highly susceptible to Leishmania amazonensis infection. However, rats are highly resistant to L. amazonensis infection due to unknown mechanisms. We use the inducible nitric oxide synthase (Nos2) gene knockout rat model (Nos2 -/- rat) to investigate the role of NOS2 against leishmania infection in rats. Our results demonstrated that diversion toward the NOS2 pathway is the key factor explaining the resistance of rats against L. amazonensis infection. Rats deficient in NOS2 are susceptible to L. amazonensis infection even though their immune response to infection is still strong. Moreover, adoptive transfer of NOS2 competent macrophages into Nos2 -/- rats significantly reduced disease development and parasite load. Thus, we conclude that the distinct L-arginine metabolism, observed in rat macrophages, is the basis of the strong innate resistance to Leishmania. These data highlight that macrophages from different hosts possess distinctive properties and produce different outcomes in innate immunity to Leishmania infections.

Common mtDNA variations at C5178a and A249d/T6392C/G10310A decrease the risk of severe COVID-19 in a Han Chinese population from Central China.

BACKGROUND: Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production, are associated with COVID-19 risk. METHODS: A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls (n = 615) and COVID-19 patients (n = 536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning. The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment. MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny. Student's t-test was used for continuous variables, and Pearson's chi-squared test or Fisher's exact test was used for categorical variables. To assess the independent effect of each mtDNA variant defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) with adjustments for possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) as determined through clinical and radiographic examinations. RESULTS: Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations (> 10% in the control population) at C5178a (in NADH dehydrogenase subunit 2 gene, ND2) and A249d (in the displacement loop region, D-loop)/T6392C (in cytochrome c oxidase I gene, CO1)/G10310A (in ND3) were associated with a reduced risk of severe COVID-19 (OR = 0.590, 95% CI 0.428-0.814, P = 0.001; and OR = 0.654, 95% CI 0.457-0.936, P = 0.020, respectively), while A4833G (ND2), A4715G (ND2), T3394C (ND1) and G5417A (ND2)/C16257a (D-loop)/C16261T (D-loop) were related to an increased risk of severe COVID-19 (OR = 2.336, 95% CI 1.179-4.608, P = 0.015; OR = 2.033, 95% CI 1.242-3.322, P = 0.005; OR = 3.040, 95% CI 1.522-6.061, P = 0.002; and OR = 2.890, 95% CI 1.199-6.993, P = 0.018, respectively). CONCLUSIONS: This is the first study to explore the association of mtDNA variants with individual's risk of developing severe COVID-19. Based on the case-control study, we concluded that the common mtDNA variants at C5178a and A249d/T6392C/G10310A might contribute to an individual's resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual's risk of developing severe COVID-19.

Changes of the Brain Causal Connectivity Networks in Patients With Long-Term Bilateral Hearing Loss.

It remains poorly understood how brain causal connectivity networks change following hearing loss and their effects on cognition. In the current study, we investigated this issue. Twelve patients with long-term bilateral sensorineural hearing loss [mean age, 55.7 ± 2.0; range, 39-63 years; threshold of hearing level (HL): left ear, 49.0 ± 4.1 dB HL, range, 31.25-76.25 dB HL; right ear, 55.1 ± 7.1 dB HL, range, 35-115 dB HL; the duration of hearing loss, 16.67 ± 4.5, range, 3-55 years] and 12 matched normally hearing controls (mean age, 52.3 ± 1.8; range, 42-63 years; threshold of hearing level: left ear, 17.6 ± 1.3 dB HL, range, 11.25-26.25 dB HL; right ear, 19.7 ± 1.3 dB HL, range, 8.75-26.25 dB HL) participated in this experiment. We constructed and analyzed the causal connectivity networks based on functional magnetic resonance imaging data of these participants. Two-sample t-tests revealed significant changes of causal connections and nodal degrees in the right secondary visual cortex, associative visual cortex, right dorsolateral prefrontal cortex, left subgenual cortex, and the left cingulate cortex, as well as the shortest causal connectivity paths from the right secondary visual cortex to Broca's area in hearing loss patients. Neuropsychological tests indicated that hearing loss patients presented significant cognitive decline. Pearson's correlation analysis indicated that changes of nodal degrees and the shortest causal connectivity paths were significantly related with poor cognitive performances. We also found a cross-modal reorganization between associative visual cortex and auditory cortex in patients with hearing loss. Additionally, we noted that visual and auditory signals had different effects on neural activities of Broca's area, respectively. These results suggest that changes in brain causal connectivity network are an important neuroimaging mark of cognitive decline. Our findings provide some implications for rehabilitation of hearing loss patients.

Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer: Results from 24 hospitals in China.

BACKGROUND: Whether regional lymphadenectomy (RL) should be routinely performed in patients with T1b gallbladder cancer (GBC) remains a subject of debate. AIM: To investigate whether RL can improve the prognosis of patients with T1b GBC. METHODS: We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China. The log-rank test and Cox proportional hazards model were used to compare the overall survival (OS) of patients who underwent cholecystectomy (Ch) + RL and those who underwent Ch only. To investigate whether combined hepatectomy (Hep) improved OS in T1b patients, we studied patients who underwent Ch + RL to compare the OS of patients who underwent combined Hep and patients who did not. RESULTS: Of the 121 patients (aged 61.9 ± 10.1 years), 77 (63.6%) underwent Ch + RL, and 44 (36.4%) underwent Ch only. Seven (9.1%) patients in the Ch + RL group had lymph node metastasis. The 5-year OS rate was significantly higher in the Ch + RL group than in the Ch group (76.3% vs 56.8%, P = 0.036). Multivariate analysis showed that Ch + RL was significantly associated with improved OS (hazard ratio: 0.51; 95% confidence interval: 0.26-0.99). Among the 77 patients who underwent Ch + RL, no survival improvement was found in patients who underwent combined Hep (5-year OS rate: 79.5% for combined Hep and 76.1% for no Hep; P = 0.50). CONCLUSION: T1b GBC patients who underwent Ch + RL had a better prognosis than those who underwent Ch. Hep + Ch showed no improvement in prognosis in T1b GBC patients. Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines, RL was only performed in 63.6% of T1b GBC patients. Routine Ch + RL should be advised in T1b GBC.

Autophagy inhibitors increase the susceptibility of KRAS-mutant human colorectal cancer cells to a combined treatment of 2-deoxy-D-glucose and lovastatin.

RAS-driven colorectal cancer relies on glucose metabolism to support uncontrolled growth. However, monotherapy with glycolysis inhibitors like 2-deoxy-D-glucose causes limited effectiveness. Recent studies suggest that anti-tumor effects of glycolysis inhibition could be improved by combination treatment with inhibitors of oxidative phosphorylation. In this study we investigated the effect of a combination of 2-deoxy-D-glucose with lovastatin (a known inhibitor of mevalonate pathway and oxidative phosphorylation) on growth of KRAS-mutant human colorectal cancer cell lines HCT116 and LoVo. A combination of lovastatin (>3.75 µM) and 2-deoxy-D-glucose (>1.25 mM) synergistically reduced cell viability, arrested cells in the G2/M phase, and induced apoptosis. The combined treatment also reduced cellular oxygen consumption and extracellular acidification rate, resulting in decreased production of ATP and lower steady-state ATP levels. Energy depletion markedly activated AMPK, inhibited mTOR and RAS signaling pathways, eventually inducing autophagy, the cellular pro-survival process under metabolic stress, whereas inhibition of autophagy by chloroquine (6.25 µM) enhanced the cytotoxic effect of the combination of lovastatin and 2-deoxy-D-glucose. These in vitro experiment results were reproduced in a nude mouse xenograft model of HCT116 cells. Our findings suggest that concurrently targeting glycolysis, oxidative phosphorylation, and autophagy may be a promising regimen for the management of RAS-driven colorectal cancers.

Detecting Lesional Granulysin Levels for Rapid Diagnosis of Cytotoxic T lymphocyte-Mediated Bullous Skin Disorders.

BACKGROUND: Bullous skin disorders are induced by different pathomechanisms and several are emergent, including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Rapid diagnostic methods for SJS/TEN or cytotoxic T-lymphocyte (CTL)-mediated bullous disorders are crucial for early treatment. Granulysin, primarily expressed by CTLs, is a specific cytotoxic protein responsible for SJS/TEN and similar skin reactions. OBJECTIVE: To assess granulysin levels in blister fluids to differentiate SJS/TEN and similar CTL-mediated bullous reactions from other autoimmune bullous disorders. METHODS: Using ELISA, we measured granulysin in blister fluids from patients with bullous skin disorders, including SJS/TEN, erythema multiforme major, bullous fixed-drug eruption, bullous lupus erythematosus, paraneoplastic pemphigus, pemphigus vulgaris, bullous pemphigoid, purpura fulminans-related bullae, and hand-foot syndrome/hand-foot-skin reactions. We compared serum and blister granulysin levels in patients with SJS/TEN presenting varying severity, monitoring serial granulysin levels from acute to late stages. RESULTS: Overall, 144 patients presenting with bullous skin disorders were enrolled. Blister granulysin levels (mean ± SD) in CTL-mediated disorders, including TEN (n = 28; 3938.7 ± 3475.7), SJS-TEN overlapping (n = 22; 1440.4 ± 1179.6), SJS (n = 14; 542.0 ± 503.2), erythema multiforme major (n = 7; 766.3 ± 1073.7), generalized bullous fixed-drug eruption (n = 10; 720.4 ± 858.3), and localized bullous fixed-drug eruption (n = 16; 69.0 ± 56.4), were significantly higher than in non-CTL-mediated bullous disorders (P < .0001), including bullous lupus erythematosus (n = 3; 22.7 ± 20.1), paraneoplastic pemphigus (n = 3; 20.3 ± 8.6), pemphigus vulgaris (n = 3; 4.4 ± 2.8), bullous pemphigoid (n = 18; 4.0 ± 2.7), purpura fulminans (n = 4; 5.9 ± 5.5), and hand-foot syndrome/hand-foot-skin reactions (n = 6; 4.6 ± 3.5). Blister granulysin levels correlated with clinical severity of SJS/TEN (P < .0001). CONCLUSIONS: Determination of blister granulysin levels is a noninvasive and useful tool for rapid differential diagnosis of SJS/TEN and other similar CTL-mediated bullous skin disorders for treatment selection.

Essential Oil from Alpiniae Zerumbet Fructus Alleviates High Glucose-induced HUVEC Injury via TXNIP Signaling Pathway / 中国实验方剂学杂志

Objective:To study the protective effect of essential oil from Alpiniae Zerumbet Fructus （EOAZF） against high glucose （HG）-induced injury of human umbilical vein endothelial cells （HUVECs） <italic>in vitro</italic>， so as to provide experimental evidence for the treatment of diabetes-induced cardiovascular diseases with EOAZF. Method:The cells were divided into the normal group， model group （25 mmol·L^-1 glucose）， positive control group （100 mg·L^-1 vitamin C）， and the low- （0.25 μg·L^-1）， medium- （1 μg·L^-1）， and high-dose （4 μg·L^-1） EOAZF groups. The HUVECs were damaged by HG. The secretion amounts of malondialdehyde （MDA）， nitric oxide （NO）， and endothelin-1 （ET-1） in HUVECs of different groups were measured to assess the protective effect of EOAZF against HG-induced injury. The effects of EOAZF on the apoptosis and reactive oxygen species （ROS） generation of HUVECs damaged by HG were detected by Annexin V-fluorescein isothiocyanate/propidium iodide （Annexin V-FITC/PI） staining and dichloro-dihydro-fluorescein diacetate （DCFH-DA） assay. The protein and mRNA expression levels of thioredoxin interacting protein （TXNIP） and thioredoxin 1 （Trx-1） were determined by Western blot and Real-time polymerase chain reaction （Real-time PCR）， followed by the measurement of total intracellular Trx-1 activity with insulin disulfide reduction method. Result:The comparison with the control group revealed that the proliferation of HUVECs in the model group was significantly inhibited and their shape was damaged. Compared with the model group， EOAZF protected HUVECs against HG-induced injury in a concentration-dependent manner. The secretion amounts of MDA and ET-1 （<italic>P</italic><0.05） in the model group were increased in contrast to those in the control group， while the NO level was decreased （<italic>P</italic><0.01）. Compared with the model group， EOAZF at all the three concentrations， especially at 4 μg·L^-1， obviously reduced the secretion of MDA and ET-1 （<italic>P</italic><0.05）， but elevated NO after HG induction （<italic>P</italic><0.05）. The cell apoptosis assay and ROS detection results demonstrated that the apoptosis and ROS level in the model group were higher than those in the control group （<italic>P</italic><0.01）. Compared with the model group， EOAZF at 4 μg·L^-1significantly lowered the ROS level and apoptosis （<italic>P</italic><0.05） of HUVECs damaged by HG. The Western blot assay and Trx-1 activity detection uncovered that the protein and mRNA expression levels of TXNIP in the model group were significantly up-regulated as compared with those in the control group （<italic>P</italic><0.05）， whereas the Trx-1 activity was decreased （<italic>P</italic><0.01）. Compared with the model group， EOAZF at 4 μg·L^-1significantly down-regulated the mRNA and protein （<italic>P</italic><0.05） expression levels of TXNIP and enhanced the total Trx-1 activity （<italic>P</italic><0.05） in HUVECs， thus suppressing the oxidative stress. Conclusion:EOAZF exerts the protective effects against HG-induced injury in HUVECs by improving the endothelial function and reducing intracellular ROS and apoptosis. Its efficacy in anti-oxidative stress may be related to the down-regulation of mRNA and protein expression levels of TXNIP and the enhancement of Trx-1 activity.

Modified Banxia Baizhu Tianmatang Combined with Acupuncture for Migraine (Wind-phlegm Upset Syndrome) Observe / 中国实验方剂学杂志

Objective:To observe theclinical efficacy of modified Banxia Baizhu Tianmatang combined with acupuncture on migraine with wind phlegm disturbance syndrome， and the regulatory effect on neurovasoactive peptide and vascular endothelial activator. Method:Two hundred and fifty patients were randomly divided into control group （75 cases） and observation group （75 cases）. Patients in Two group got acupuncture for 6 times， 1 time/day， after a day of rest， they got placebogranules of Banxia Baizhu Tianmatang， 10 g/time， 2 times/day. Patients in observation group got Banxia Baizhu Tianmatang， 1 dose/day， and also the same acupuncture with the therapyof control group. And the treatment lasted for 4 weeks. At the half， 1^st， 2^nd， 6^th， 12^th， 24^th， and 48^th hour after treatment， VAS were scored， rate of pain relief within 6， 12， and 24 hours， disappearance rate and recurrence rate of pain within 72 hours， migraine attack times， headache duration and headache degree before 4 weeks of treatment， during the treatment and after the treatment were recorded. Before and after treatment， accompanying symptoms， wind phlegm disturbance syndrome， headache impact test version-6 （HIT-6） and the migraine disability assessment questionnaire （MIDAS） were scored. And levels of calcitonin gene-related peptide （CGRP）， nitric oxide （NO）， endothelin-1 （ET-1）， pituitary adenylate cyclase activating peptide （PACAP）， S100B protein， substance P（SP）， von Willebrand factor （vWF） and fibrinogen （FIB） were detected. And safety was evaluated. Result:VAS in two groups decreased at different time points （<italic>P<</italic>0.01）， and VAS in observation group at 6^th， 12^th， 24^thand 48^th hour after treatment were lower than those in control group （<italic>P<</italic>0.01）. The rate of pain relief in observation group at 6^th and 12^th hours after treatment and the disappearance rate of pain at 72^th hour were 67.14%（47/70）， 87.14% （61/70） and 92.86% （65/70）， which were higher than 50.00% （34/68）， 70.59% （48/68） and 79.41% （54/68） in control group. The recurrence rate of pain in observation group was 21.43% （15/70）， which was lower than 39.71% （27/68） in control group （<italic>P<</italic>0.05）. During the treatment and drug withdrawal， times of migraine attack， headache duration and headache degree were all less than those in control group （<italic>P<</italic>0.01）. Scores of accompanying symptoms， wind phlegm disturbance syndrome， HIT-6 and MIDAS were all lower than those in control group （<italic>P<</italic>0.01）. The clinical effect was better than that in control group （<italic>Z</italic>=2.106， <italic>P<</italic>0.05）. Levels of CGRP， PACAP， S100B protein， SP， ET-1， vWF and FIB were lower than those in control group， while level of NO was higher than control group （<italic>P<</italic>0.01）. Conclusion:Modified Banxia Baizhu Tianmatang combined with acupuncture had a better instant analgesic effect， with a significant effect on continuing analgesia and reducing headache recurrence. It can also alleviate migraine symptoms and accompanying symptoms， andreduce the impact of migraine on daily life and the degree of disability. Its mechanism may be related to the regulation of neurovasoactive peptides and vascular endothelial substances. It is worth for further study.

Clinical features and mortality-related factors of extensive burns among young adults: the Kunshan disaster experience.

BACKGROUND: The aim of the study was to identify the clinical features and the factors associated with burn induced mortality among young adults after exposure to indoor explosion and fire. METHODS: This is an observational study which included burn patients who were admitted to eighteen ICUs after a fire disaster. Epidemiologic and clinical characteristics, as well as therapy were recorded. The primary outcome was 90-day mortality. The mortality-related factors were also analyzed. RESULTS: There were 167 burn patients enrolled in the study, the median age was 38 years, 62 (37.1%) patients died within 90 days. Seventy-one percent of patients had a burn size ≥90% TBSA, and 73.7% of patients had a full-thickness burn area above 50% TBSA. The survivors had lower Baux scores, and received earlier escharectomy and autologous skin grafts. The 50% mortality rates (LA50s) for burn size and full-thickness burn area were 95.8% and 88.6% TBSA, respectively. The multivariate analysis showed that full-thickness burn area over 50% TBSA and residual burned surface area (RBSA)/TBSA at 28 days were strong predictors of mortality among burn patients (odds ratio 2.55; 95% CI, 1.01 to 6.44, P=0.047; odds ratio 1.07; 95% CI, 1.04 to 1.09, P<0.001). The ROC curve-based cut-off values of RBSA/TBSA at 28 days for predicting 90-day mortality were 62.5%. CONCLUSIONS: Burn size and full-thickness burn area were the main risk factors for poor outcome in patients with extensive burns. Earlier escharectomy and autologous skin grafts may improve outcomes.