Menaquinone-4 exerts a protective effect against carbon tetrachloride-induced acute liver injury in mice by alleviating ferroptosis / 临床肝胆病杂志

ObjectiveTo investigate whether menaquinone-4 （MK-4） can exert a protective effect against carbon tetrachloride （CCl4）-induced acute liver injury （ALI） in mice by alleviating ferroptosis. MethodsAfter adaptive feeding， adult male ICR mice， aged 8 weeks， were divided into Control group， MK-4 group， CCl4 model group （6-hour， 12-hour， and 24-hour）， and MK-4+CCl4 group （6-hour， 12-hour， and 24-hour）， with 6 mice in each group. The mice in the Control group were given intraperitoneal injection of an equal dose of corn oil； the mice in the MK-4 group were given intraperitoneal injection of 40 mg/kg MK-4 solution， followed by an equal dose of corn oil after 1 hour； the mice in the MK-4+CCl4 group （6-hour， 12-hour， and 24-hour） were given intraperitoneal injection of 40 mg/kg MK-4 solution， and after 1 hour， the mice in this group and the CCl4 model group （6-hour， 12-hour， and 24-hour） were given intraperitoneal injection of 0.3 mL/kg CCl4 solution， with samples collected at 6， 12， and 24 hours. HE staining was used to observe the pathological changes of mouse liver； Prussian blue staining was used to observe iron accumulation in liver tissue； a biochemical analyzer was used to measure the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）； related kits were used to measure the levels of tissue iron content and the oxidative stress indices malondialdehyde （MDA） and glutathione （GSH） in liver homogenate； RT-PCR was used to measure the expression levels of ferroptosis marker genes （acyl-CoA synthetase long-chain family member 4 ［ACSL4］， prostaglandin-endoperoxide synthase 2 ［PTGS2］， and glutathione peroxidase 4 ［GPX4］） and iron metabolism-related genes （hemojuvelin ［HJV］， transferrin receptor 1 ［TFR1］， and ferroportin ［FPN］）， and Western blot was used to measure the protein expression level of GPX4. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsIn the aging study， compared with the Control group， the CCl4 model group （6-hour， 12-hour， and 24-hour） had significant increases in liver weight coefficient and the serum levels of ALT and AST （all P<0.05）， and HE staining also showed that liver injury gradually aggravated over time. Meanwhile， compared with the CCl4 model group （6-hour， 12-hour， and 24-hour）， the MK-4+CCl4 （12-hour） group had significant reductions in liver weight coefficient and the serum levels of ALT and AST （all P<0.05）， with a reduction in the necrotic area of liver tissue， and therefore， 12-hour mouse tissue samples were used for detection in the following study. Compared with the Control group， the CCl4 group had a significant increase in MDA and a significant reduction in GSH （both P<0.05）， and compared with the CCl4 group， the MK-4+CCl4 group had a significant reduction in MDA and a significant increase in GSH （both P<0.05）. Compared with the Control group， the CCl4 group had significant increases in the key ferroptosis indices ASCL4 and PTGS2 and a significant reduction in GPX4 （all P<0.05）； compared with the CCl4 group， the MK-4+CCl4 group had significant reductions in the mRNA expression levels of ASCL4 and PTGS2 and a significant increase in the mRNA expression level of GPX4 （all P<0.05）. Western blotting showed that compared with the Control group， the CCl4 group had a significant reduction in the protein expression level of GPX4 （P<0.05）， and compared with the CCl4 group， the MK-4+CCl4 group had a significant increase in the protein expression level of GPX4 （P<0.05）. Prussian blue staining showed that compared with the Control group， the CCl4 group had a significant increase in iron accumulation； after MK-4 intervention， compared with the CCl4 group， the MK-4+CCl4 group had a significant reduction in iron accumulation. As for the measurement of iron metabolism genes in mouse liver， compared with the Control group， the CCl4 group had a significant increase in iron content， significant reductions in the mRNA expression levels of FPN and HJV， and a significant increase in the mRNA expression level of TFR1 （all P<0.05）； after protection with MK-4， there was a significant reduction in iron content， significant increases in the mRNA expression levels of FPN and HJV， and a significant reduction in the mRNA expression level of TFR1 （all P<0.05）. ConclusionMK-4 intervention in advance can alleviate CCl4-induced ALI in mice， possibly by inhibiting ferroptosis and improving the expression of iron metabolism-related genes in mouse liver.

Association between endoplasmic reticulum stress and ferroptosis in liver diseases / 临床肝胆病杂志

Research on the pathogenesis of liver diseases has attracted great attention. Endoplasmic reticulum stress (ERS) is a self-protective mechanism of cells, but sustained and severe ERS can induce apoptosis, autophagy, and ferroptosis, among which ferroptosis has been a research hotspot in recent years. Ferroptosis is mainly characterized by the accumulation of iron-dependent lipid peroxides and plays a key role in the development and progression of liver diseases, but there are currently few studies on the involvement of ERS in ferroptosis in liver diseases. This article summarizes the research advances in ERS-related signaling pathways, the mechanism of ferroptosis, and the involvement of ERS in liver diseases, so as to provide more ideas for research on the treatment of liver diseases.

Effects of physical activity on mental and behavioral health and functioning for college students: a systematic review using ICF / 中国康复理论与实践

ObjectiveTo construct the physical activity intervention effect category and framework for college students with mental and behavioral health and functioning problems based on International Classification of Functioning, Disability, and Health (ICF). MethodsThe typical mental and behavioral health and functioning condition of college students were systematically analyzed using ICF. Relevant literatures about the health and functioning outcomes of college students participating in physical activity were retrieved from the databases of PubMed, Web of Science, EBSCO, and CNKI, from the establishment to August 20th, 2022, and reviewed systematically. ResultsTen English literatures were included, involving ten randomized controlled trials with 848 participants aged 15 to 34 years from seven countries, mainly from the journals of rehabilitation science, sports rehabilitation, rehabilitation psychology and health psychology, and were mainly published after 2016. The typical mental and behavioral health and functioning problems of college students mainly focused on stress, anxiety, depression, sleep disorders, learning fatigue, mobile phone addiction, alcohol drinking disorder, sedentary behavior and physical inactivity. Physical activity interventions included Biodanza, Hatha Yoga, Tai Chi, basketball, Baduanjin, cycling, swimming, roller skating, baseball, skill training, stretching exercise, resistance training, and aerobic exercise, etc. The frequency of interventions was mainly a long-term (four to 14 weeks, one to three times per week) program of high-, moderate-, or low-intensity physical activity. The health outcomes included improving cognitive function, relieving stress, anxiety, depression and learning fatigue, reducing negative automatic thinking, enhancing mindfulness, reducing loneliness and deficiency, improving sleep quality, improving upper limb muscle endurance; promoting the development of exercise habits, increasing physical activity participation, improving activity performance and academic performance, reducing sedentary behavior, drinking behavior and problematic mobile phone use; increasing social interaction, improving health perception and psychosocial function, enriching and improving recreation and campus life, and improving the quality of interpersonal relationships, quality of life and well-being. ConclusionA conceptual framework of physical activity participation of college students with mental and behavioral health and functioning problems is constructed using ICF. The typical mental and behavioral health and functioning problems of college students are mainly classified as mental health and functioning problems, behavioral health and functioning problems. The intervention types of physical activity are divided into physical fitness category, skill category, sports category and combination category. Health outcomes can be reflected in three dimensions: physical and mental health, activity and behavioral health, and overall functioning and quality of life.

A single-center research of peroral endoscopic myotomy for primary achalasia in patients over 60 years old / 中华消化内镜杂志

Objective:To explore the therapeutic effect of peroral endoscopic myotomy (POEM) for primary achalasia (AC) in patients aged over 60 years.Methods:Data of 146 patients aged ≥60 years (the elderly group) and 146 patients aged 18-59 years (the adult group) who received POEM from November 2010 to September 2019 at the Digestive Endoscopy Center of PLA General Hospital were retrospectively analyzed. Baseline data, surgery data, surgery-related complications and surgery-related efficacy were compared.Results:There was no significant difference in gender, Ling classification, HRM classification or previous treatment between the two groups ( P>0.05). All 292 patients successfully underwent POEM surgery. The clinical success (Eckardt score ≤3) rates in the elderly group and the adult group were 96.33% (105/109) and 96.77% (90/93), respectively with no significant difference between the two groups ( χ2=0.030， P>0.05). There was no significant difference in the length of myotomy between the two groups (7.09±2.49 cm VS 7.12±2.24 cm， t=0.472， P>0.05). Complications occurred in 26 cases (17.81%) in the elderly group and 21 cases (14.38%) in the adult group with no significant difference between the two groups ( χ2=0.634， P>0.05). There was no significant difference in the postoperative hospital stay (12.61±9.69 days VS 11.00±4.43 days, t=1.825, P>0.05) or the incidence of gastroesophageal reflux [43.33% (13/30) VS 51.52% (17/33), χ2=0.422, P>0.05] between the elderly group and the adult group. Conclusion:The efficacy of POEM for AC patients over 60 years old is equivalent to that of adult patients, and the incidence of complications is similar. POEM is safe and effective for AC patients over 60 years old.

Analysis of high-risk behaviors related to HIV infection in men who have sex with men recruited by different methods / 中华皮肤科杂志

Objective:To analyze high-risk behaviors related to HIV infection in men who have sex with men (MSM) recruited by different methods in Zhenjiang city, and to provide a reference for precise prevention and control of acquired immunodeficiency syndrome (AIDS) .Methods:From April to June in 2020, MSM in Zhenjiang city were recruited as research subjects through the center for disease control and prevention (CDC) voluntary counseling and testing (VCT) clinic and community-based organizations (CBOs) . Information such as demographic characteristics, drug abuse, HIV testing history and high-risk sexual behavior were collected through a unified questionnaire survey. Chi-square test or Fisher′s exact test was used to analyze differences in relevant characteristics of MSM recruited by different methods.Results:A total of 641 MSM were recruited by the two methods, including 442 (68.95%) recruited from CBOs and 199 (31.05%) from CDC; the proportion of MSM aged under 20 years was significantly higher in the CBO group (6.56%) than in the CDC group (1.01%, χ2 = 9.20, P = 0.002) ; the proportions of MSM receiving health education information on potential hazards of drug use from professional health institutions and new network media were significantly higher in the CDC group (7.54% [15/199], 16.58% [33/199], respectively) than in the CBO group (3.39% [15/442], χ2 = 5.28, P = 0.022; 9.50% [42/442], χ2 = 6.66, P = 0.010) . In terms of characteristics of sexual behavior, the CBO group showed significantly increased proportions of individuals having group sex (25.21%, 30 cases) and those having unprotected sexual intercourse with women (47.51%, 210 cases) compared with the CDC group (7.50% [6 cases], χ2 = 10.13, P = 0.001; 27.64% [55 cases], χ2 = 22.35, P < 0.001, respectively) , but significantly decreased proportions of heterosexuals (2.04%, 9 cases) , individuals unknowing about the HIV status of sexual partners (22.40%, 99 cases) and those having unprotected anal sex with men (39.82%, 176 cases) compared with the CDC group (6.53% [13 cases], χ2 = 8.37, P = 0.004; 39.70% [79 cases], χ2 = 20.48, P < 0.001; 57.29% [114 cases], χ2 = 16.90, P < 0.001, respectively) . Compared with the CDC group, the CBO group showed significantly decreased proportions of individuals ever having an HIV test (74.43% [329 cases] vs. 80.90% [161 cases], χ2 = 3.19, P = 0.074) and those getting the latest HIV test from CDC (23.10% [76 cases] vs. 57.14% [92 cases], χ2 = 99.41, P < 0.001) , as well as decreased prevalence of HIV infection (5.20% [23 cases] vs. 13.07% [26 cases], χ2 = 21.85, P < 0.001) . Conclusions:The MSM recruited from CBO and CDC are complementary in terms of demographics and behaviors, and can represent the general MSM population. Specific prevention and control measures for AIDS should be taken according to different characteristics of the MSM population.

A nomogram for predicting lymph node metastasis in early gastric cancer / 中华胃肠外科杂志

Objective: To explore the independent risk factors of lymph node metastasis (LNM) in early gastric cancer, and to use nomogram to construct a prediction model for above LNM. Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) primary early gastric cancer as stage pT1 confirmed by postoperative pathology; (2) complete clinicopathological data. Exclusion criteria: (1) patients with advanced gastric cancer, stump gastric cancer or history of gastrectomy; (2) early gastric cancer patients confirmed by pathology after neoadjuvant chemotherapy; (3) other types of gastric tumors, such as lymphoma, neuroendocrine tumor, stromal tumor, etc.; (4) primary tumors of other organs with gastric metastasis. According to the above criteria, 1633 patients with early gastric cancer who underwent radical gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital First Medical Center from December 2005 to December 2020 were enrolled as training set, meanwhile 239 patients with early gastric cancer who underwent gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital Fourth Medical Center from December 2015 to December 2020 were enrolled as external validation set. Risk factors of LNM in early gastric cancer were identified by using univariate and multivariate logistic regression analyses. A nomogram prediction model was established with significant factors screened by multivariate analysis. Area under the receiver operating characteristic curve (AUC) was used for assessing the predictive value of the model. Calibration curve was drawn for external validation. Results: Among 1633 patients in training set, the mean number of retrieved lymph nodes was 20 (13-28), and 209 patients (12.8%) had lymph node metastasis. Univariate analysis showed that gender, resection range, tumor location, tumor morphology, lymph node clearance, vascular invasion, lymphatic cancer thrombus, tumor length, tumor differentiation, microscopic presence of signet ring cells and depth of tumor invasion were associated with LNM (all P<0.05). Multivariate analysis revealed that females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa, and poor differentiation were independent risk factors for LNM in early gastric cancers (all P<0.05). Receiver operating characteristic curve indicated that AUC of training set was 0.818 (95%CI: 0.790-0.847) and AUC of external validation set was 0.765 (95%CI: 0.688-0.843). The calibration curve showed that the LNM probability predicted by nomogram was consistent with the actual situation (C-index: 0.818 in training set and 0.765 in external validation set). Conclusions: Females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa and poor differentiation are independent risk factors for LNM of early gastric cancer. The establishment of a nomogram prediction model for LNM in early gastric cancer has great diagnostic value and can provide reference for treatment selection.

Clinical study of soluble thrombomodulin and urinary neutrophil gelatinase-associated lipocalin in early prediction of sepsis-induced acute kidney injury / 中华急诊医学杂志

Objective:To compare the early diagnostic value of the indicators of endothelial injury, renal injury, inflammation and coagulation in patients with sepsis-induced acute kidney injury (AKI).Methods:A retrospective study was performed on 119 patients with sepsis from February 2017 to March 2018. Lab tests were performed on patients at admission, which included:ing soluble thrombomodulin (sTM), tissue plasminogen activators and inhibitors (t-PAI-C), antithrombin III (AT-III), thrombin-antithrombin (TAT) complex, plasmin-alpha 2, plasmin inhibitor complex (PIC), fibrin degradation product (FDP), fibrinogen (FIB), D-Dimer, prothrombin time (PT), prothrombin time international normalized ratio (PT-INR), procalcitoni (PCT), white blood cell (WBC), neutrophil (Neu), and platelet count (PLT). The receiver-operating characteristic curve was used to analyze the predictive value of the above indicators, and logistic regression analysis was used to analyze the risk factors of sepsis-induced AKI. A prospective study was conducted from April 2018 to September 2018 and 46 patients were enrolled. The lab tests results retrieved including sTM, t-PAI-C, FDP, AT-III, TAT, PIC, FIB, D-Dimer, PT, PCT, serum cystatin C (Cys C), urine albumin (microalbumin) and albumin to creatinine ratio (ACR), urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary N-acetyl-beta-glucosaminidase (uNAG), and urinary retinol-binding protein (uRBP). As same with the previous group, the receiver-operating characteristic curve was used to analyze the diagnostic value of the above indicators, and logistic regression Was used to analyze the risk factors of sepsis-induced AKI.Results:(1) In the retrospective study: sTM, D-Dimer, PCT, PT, and PT-INR were statistically different. sTM, D-Dimer, PCT, PT, and PT-INR had a good diagnostic value for septis-induced AKI, among which, sTM had a highest diagnostic value (AUC: 0.857; 95% CI: 0.790, 0.924), better sensitivity (64.4%) and specificity (91.8%). The high expression of sTM and history of chronic kidney disease were independent risk factors for septis-induced AKI.(2) In the prospective study: PCT, sTM , Cys C, and uNGAL were statistically different. PCT, sTM, Cys C, uNGAL showed good predictive features for septis-induced AKI. sTM had the highest sensitivity (>0.999) while uNGAL had the highest specificity (0.800). The high expression of sTM was an independent risk factor for septis-induced AKI. Conclusions:sTM and uNGAL represent endothelial injury and renal tubular injury respectively. sTM is an independent risk factor of sepsis-induced AKI.

Application of Logistic regression and decision tree analysis in prediction of acute myocardial infarction events / 浙江大学学报·医学版

OBJECTIVE: To evaluate the application of decision tree method and Logistic regression in the prediction of acute myocardial infarction (AMI) events. METHODS: The clinical data of 295 patients, who underwent coronary angiography due to angina or chest pain with unidentified causes in Zhejiang provincial People's Hospital during October 2018 and April 2019, were retrospectively analyzed. Fifty five patients were identified as AMI. Logistic regression and decision tree methods were performed to establish predictive models for the occurrence of AMI, respectively; and the models created by decision tree analysis were divided into Logistic regression-independent model (Tree 1) and Logistic regression-dependent model (Tree 2). The performance of Logistic regression and decision tree models were compared using the area under the receiver operating characteristic (ROC) curve. RESULTS Logistic regression analysis showed that history of coronary artery disease, multi-vessel coronary artery disease, statin use and apolipoprotein (ApoA1) level were independent influencing factors of AMI events (all P<0.05). Logistic regression-independent decision tree model (Tree 1) showed that multi-vessel coronary artery disease was the root node, and history of coronary artery disease, ApoA1 level (the cutoff value:1.314 g/L) and anti-platelet drug use were descendant nodes. In Logistic regression-dependent decision tree model (Tree 2), multi-vessel coronary artery disease was still the root node, but only followed by two descendant nodes including history of coronary artery disease and ApoA1 level. The area under the curve (AUC) of ROC of Logistic regression model was 0.826, and AUCs of decision tree models were 0.765 and 0.726, respectively. AUC of Logistic regression model was significantly higher than that of Tree 2 (95% CI=0.041-0.145, Z=3.534, P<0.001), but was not higher than that of Tree 1 (95% CI=-0.014-0.121, Z=-1.173, P>0.05). CONCLUSIONS The predictive value for AMI event was comparable between Logistic regression-independent decision tree model and Logistic regression model, implying the data mining methods are feasible and effective in AMI prevention and control.

Progresses of echocardiography in evaluation on cardiomyopathy / 中国医学影像技术

Cardiomyopathy is a type of diseases with complex etiology and varied manifestations. Traditional echocardiography is the first-line examination method for screening and diagnosing cardiomyopathy, which has the advantages of non-invasion and convenience. In recent years, new techniques of echocardiography can provide more information for diagnosis of cardiomyopathy. The progresses of echocardiography in evaluation of cardiomyopathy were reviewed in this article.

Mitochondrial Autophagy and NLRP3 Inflammasome in Pulmonary Tissues from Severe Combined Immunodeficient Mice after Cardiac Arrest and Cardiopulmonary Resuscitation / 中华医学杂志(英文版)

<p><b>Background</b>The incidence of cancer, diabetes, and autoimmune diseases has been increasing. Furthermore, there are more and more patients with solid organ transplants. The survival rate of these immunocompromised individuals is extremely low when they are severely hit-on. In this study, we established cardiac arrest cardiopulmonary resuscitation (CPR) model in severe combined immunodeficient (SCID) mice, analyzed the expression and activation of mitochondrial autophagy and NLRP3 inflammasome/caspase-1, and explored mitochondrial repair and inflammatory injury in immunodeficiency individual during systemic ischemia-reperfusion injury.</p><p><b>Methods</b>A potassium chloride-induced cardiac arrest model was established in C57BL/6 and nonobese diabetic/SCID (NOD/SCID) mice. One hundred male C57BL/6 mice and 100 male NOD/SCID mice were randomly divided into five groups (control, 2 h post-CPR, 12 h post-CPR, 24 h post-CPR, and 48 h post-CPR). A temporal dynamic view of alveolar epithelial cells, macrophages, and neutrophils from bronchoalveolar lavage fluid (BALF) was obtained using Giemsa staining. Spatial characterization of phenotypic analysis of macrophages in the lung interstitial tissue was analyzed by flow cytometry. The morphological changes of mitochondria 48 h after CPR were studied by transmission electron microscopy and quantified according to the Flameng grading system. Western blotting analysis was used to detect the expression and activation of the markers of mitochondrial autophagy, NLRP3 inflammasome, and caspase-1.</p><p><b>Results</b>(1) In NOD/SCID mice, macrophages were disintegrated in BALF, and many alveolar epithelial cells were shed at 48 h after resuscitation. Compared with C57BL/6 mice, the ratio of macrophages/total cells peaked at 12 h and was significantly higher in NOD/SCID mice (31.17 ± 4.13 vs. 49.69 ± 2.43, t = 14.46, P = 0.001). After 24 h, the results showed a downward trend. Furthermore, a large number of macrophages were disintegrated in the BALF. (2) Mitochondrial autophagy was present in both C57BL/6 and NOD/SCID mice after CPR, but it began late in the NOD/SCID mice. Compared with C57BL/6 mice, phos-ULK1 (Ser) expression was significantly lower at 2 h and 12 h after CPR (2 h after CPR: 1.88 ± 0.36 vs. 1.12 ± 0.11, t = -1.36, P < 0.01 and 12 h after CPR: 1.52 ± 0.16 vs. 1.05 ± 0.12, t = -0.33, P < 0.01), whereas phos-ULK1 (Ser) expression was significantly higher at 2 h and 12 h after CPR in NOD/SCID mice (2 h after CPR: 1.28 ± 0.12 vs. 1.69 ± 0.14, t = 1.7, P < 0.01 and 12 h after CPR: 1.33 ± 0.10 vs. 1.94 ± 0.13, t = 2.75, P < 0.01). (3) Furthermore, NLRP3 inflammasome/caspase-1 activation in the pulmonary tissues occurred early and for only a short time in C57BL/6 mice, but this phenomenon was sustained in NOD/SCID mice. The expression of the NLRP3 inflammasome increased modestly in the C57 mice, but the increase was higher in the NOD/SCID mice than in the C57BL/6 mice, especially at 12, 24, 48 h after CPR (48 h after CPR: 1.46 ± 0.13 vs. 2.97 ± 0.19, t = 5.34, P = 0.001). The expression of caspase-1-20 generally followed the same pattern as the NLRP3 inflammasome.</p><p><b>Conclusions</b>There is a regulatory relationship between the NLRP3 inflammasome and mitochondrial autophagy after CPR in the healthy mice. This regulatory relationship was disturbed in the NOD/SCID mice because the signals for mitochondrial autophagy occurred late, and NLRP3 inflammasome- and caspase-1-dependent cell injury was sustained.</p>

Neuroprotective effects of saffron on chronic focal cerebral ischemia through inhibiting glial scar formation in rats / 中国药理学与毒理学杂志

OBJECTIVE To explore the neuro-protective effects of saffron (Crocus satius L.) on chronic focal cerebral ischemia in rats.METHODS SD rats were randomly divided into 6 groups:sham control group,MCAO group,edaravone group and saffron 30,100,300 mg·kg-1groups.Focal cerebral ischemia was induced by middle cerebral artery occlusion(MCAO).Saffron was administered orally by once daily from 2 h to 42 d after ischemia. At 42 d after cerebral ischemia, neurological deficit score, spontaneous activity test,elevated plus maze test,marble burying test and novel objective recognition test were used to evaluate the effects of saffron on the behevioural change. Infarct volume, survival neuron density, activated astrocyte number, and the thickness of glial scar were also detected. GFAP expression and inflammatory cytokine contents in ischemic peripheral region were detected by Western blot and ELISA,separately.RESULTS Saffron(100,300 mg·kg-1)improved the body weight decrease, neurological deficit and spontaneous activity. Saffron (30-300 mg·kg- 1) increased the traveled distance ratio and total time in open arm, decreased the buried marble number, which indicated that saffron could ameliorate anxiety- and depression-like behaviors. Saffron (100, 300 mg·kg-1)improved the learning and memory function,which manifested by increased discrimination ratio(DR)and discrim-ination index (DI) in T2test. The results of toluidine blue found saffron treatment (100, 300 mg·kg-1) decreased the infarct volume and increased the neuron density in cortex and hippocampal.The activated astrocyte number,the thickness of glial scar and GFAP expression in ischemic peripheral region decreased after saffron. Saffron (100, 300 mg·kg-1) decreased the contents of IL-6 and IL-1β, increased the content of IL-10 in ischemic peripheral region.CONCLUSION Saffron exerted neuro-protective effects on chronic focal cerebral ischemia,which could be related with inhibiting the activation of astrocyte and glial scar,following with the decrease of inflammatory reaction.

Comparison of corneal biomechanical parameters between keratoconus and laser corneal refractive surgery / 眼科新进展

Objective To measure biomechanical parameters of the cornea after keratoconus and laser corneal refractive surgery by Scheimpflug noncontact tonometry (Corvis ST),and analyze the changes and differences in these parameters.Methods From April 2011 to November 2016,63 patients (96 eyes) with clinically diagnosed as keratoconus were selected as the keratoconus group,and 60 patients (120 eyes) underwent laser corneal refractive surgery between November 2016 to March 2017 were selected as postoperative cornea group,and totally 51 healthy person (102 eyes) who received physical examination during the same period were selected as healthy cornea group.Scheimpflug noncontact tonometry (Corvis ST) was performed to measure the length of appl 1,length of appl 2,velocity of appl 1,velocity of appl 2,maximum deformation amplitude,apex distance and radius of curvature in the three groups.Total comparison of biomechanical parameters was performed using ANOVA test among the three groups,while pairwise comparison was performed to analyze the difference of these parameters by SNK methods.Pearson or Spearman correlation analysis was applied to assess the differences in corneal morphological and biomechanical parameters.Results There was no significant difference in length of appl 1,length of appl 2 of the three groups (all P ＞ 0.05).And velocity of appl 1 in the keratoconus group was significantly higher than that of the healthy cornea group [(0.189 ± 0.230) m · s-1 vs.(0.151 ± 0.017)m · s-1] (P ＜ 0.05).As for velocity of appl 2,the keratoconus group was larger than the healthy cornea group,both which were larger than the postoperative cornea group,and the differences were significant (all P ＜ 0.05).And this was true of maximum deformation amplitude in the three groups,with the significant differences(all P ＜ 0.05).The apex distance in the keratoconus group was significantly longer than that in the healthy cornea group (P ＜ 0.05).The radius of curvature of the keratoconus group,postoperative cornea group and healthy cornea group were (5.696 ± 0.881) mm,(7.129 ± 0.681) mm and (7.012 ± 0.728) ram,respectively,which approached significant differences(all P ＜ 0.05).There was significant correlation between the anterior surface refractive power (Km) and apex distance and radius of curvature in the keratoconus group (r =-0.205,0.1 84;P =0.023,0.041),and maximum posterior surface elevation had a statistically significant correlation with velocity of appl 2,maximum deformation amplitude and radius of curvature (r =-0.579,-0.307,0.256,P =0.022,0.002,0.000).For the eyes in the postoperative cornea group,there were no significance correlation between the anterior surface refractive power (Km) and biomechanical properties (P ＞ 0.05),but significant correlation with length of appl 2 (r =-0.297,P =0.026).There were no significant correlation between maximum posterior surface elevation and biomechanical properties (P ＞ 0.05).Conclusion The corneal biomechanical parameters are decreased in eyes after keratoconus and laser corneal refractive surgery,and Corvis ST can become an auxiliary examination tool for earlier diagnosis of secondary keratoconus after corneal refractive surgery.

A clinical study of sepsis-related coagulation disorder / 中华急诊医学杂志

Objective To study in the correlation of the laboratory markers of coagulation,fibrinolysis and thrombosis in patients with sepsis and SOFA score,the procalcitonin (PCT) concentration and seven-day survival rate.Methods From February 2017 to March 2018,119 patients with sepsis admitted in ICU and another 119 patients with non-sepsis undergoing selective surgery were enrolled as control in this study.APTT (activated partial thromboplastin time),PT-INR (prothrombin time-international normalized ratio),FIB (fibrinogen),AT-Ⅲ (antithrombin Ⅲ),D-Dimer,FDP (fibrinogen degradation products),sTM (soluble thrombomodulin),TAT (thrombin antithrombin complex),PIC (plasmin-a2 plasminogen inhibitor complex) and t-PAI-C (tissue plasminogen activator and its inhibitor complex),were simultaneously monitored at admission.The correlation between the given laboratory markers mentioned and SOFA score,the PCT concentration and seven-day survival rate were analyzed with the Spearman correlation analysis.Results (① In the patients with sepsis,a positive correlation between SOFA score and sTM,t-PAI-C,TAT respectively was found,and a negative correlation between SOFA score and PLT (platelet count) was observed,and no correlation between SOFA score and PIC was noticed.(②) A positive correlation between PCT and sTM,t-PAI-C respectively was significant,a negative correlation between PCT and PLT was marked,and no correlation between PCT and AT-Ⅲ,TAT,PIC respectively was found.(③) A negative correlation between seven-day survival rate and sTM,t-PAI-C and TAT respectively was obvious,a positive correlation between seven-day survival rate and AT-Ⅲ,PLT respectively was occurred,and no correlation between seven-day survival rate and PIC was determined.Conclusions Soluble thrombomodulin (sTM),thrombin-antithrombin (TAT),antithrombin Ⅲ (AT-Ⅲ) and tissue plasminogen activator inhibitor complex (t-PAI-c) were good clinical monitoring indicators of coagulation disorder in patients with sepsis,which were the representative of the endothelial cell damage with highly activated coagulation,relatively insufficient anti-coagulation function and poor fibrin degradation ability.These were good adjuvants to PLT,INR and APTT for core diagnostic criteria of coagulation disorder in sepsis.

Clinical retrospective analysis of 138 cases of multiple myeloma / 中华急诊医学杂志

Objective To analysis of multiple myeloma (MM) and non-MM patients with the same clinical manifestations but significant differences in laboratory findings at the first visit to the Emergency Medicine Department suggesting that patient should be rule out the possibilities of suffering from MM by the attending physicians engaging in a specialty other than hematology as soon as possible to avoid misdiagnosis of MM.Methods Retrospective analysis of clinical features of MM cases from February 2013 to December 2016.Patients with renal dysfunction (serum creatinine ≥ 177 mmol/L),infection,bone pain and anemia were divided into four groups.The non-MM patients with the same clinical symptoms were enrolled as control group.SPSS22.0 and Medcalce 15.10 software were used for analyzing the distinct difference and diagnostic validity of routine laboratory tests in patients with MM and non-MM.Results ①The patients with serum creatinine≥ 177 mmol/L,and unexplained renal insufficiency with blood Ca2+ ＞ 2.39mmol/L,ALB ≤ 30.31 g/L and Hb≤84 g/L should be investigated the possibility of MM.②The patient with poor response to the conventional treatment and unexplained infection with IgM ＜0.42 g/L and ALB≤32.7 g/L or ESR ＞ 82 mm/h and Hb ＜ 100 g/L should be investigated the possibility of MM.③The male patients with the first symptom in bone and joint pain associated with bone damage with urinary protein and blood,and the emergence of Ca2+ ＞ 2.39 mmol/L,ALB ＜ 37.5 g/L,Hb ＜ 104 g/L and TT ＞ 19.8 s were suggested to detect MM.④The poor respose to conventional treatment,unexplained anemia (Hb≤90 g/L),IgM ＜ 0.51 g/L,ALB ＜ 34.1 g/L and GLB ＞ 46.4 g/L suggested to detect MM.Conclusions On the basis of symptoms such as renal insufficiency,infection,bone pain,anemia,routine blood laboratory findings of high calcium,low IgM,low albumin,and high globulin,it was recommended that bone marrow biopsy be made to detect MM.

Application of Cost-Utility Analysis in Health Area of China:a Systematic Review / 中国药房

OBJECTIVE:To evaluate the application of cost-utility analysis in health area of China in recent year. METH-ODS:From CNKI,Wanfang and VIP database,settingcost utilityorcost-utilityastitleorkeyword,related literatures were retrieved during Jan. 2011-Dec. 2015,with subject field ofmedical science and technologyin CNKI,medical sciencein Wanfang database,clinical medicineChinese medicinepreclinical medicinepreventive medicine hygieneorpharmacyin VIP. The comprehensive evaluation involved research design,research perspective,cost measurement,utility index and measure-ment method,cost-utility analysis index,discount and sensitivity analysis. RESULTS:A total of 31 literatures meeting inclusion cri-teria were selected,including 12 prospective studies,9 retrospective studies,9 Markov model studies,1 mixed study. Thirteen lit-eratures worked in medical institutions. Seven literatures explicitly mentioned research perspective;most literatures only measured direct cost(19 literatures)and adopted QALY as utility index(27 literatures). Twenty eight literatures described measurement meth-od of utility index(direct measurement,indirect measurement or literature method)in detail. More than half(16 literatures)analyzed cost-utility by using cost-utility ratio(CUR);7 literatures adopted incremental cost-utility ratio(ICUR)and 6 literatures adopted both CUR and ICUR. Five literatures used the threshold of ICUR. Eleven literatures described discount,and the majority was Markov mod-el study. Sensitivity analysis was conducted in 16 literatures,among which 11 literatures adopted single factor analysis. The most com-monly involved influential factor was cost,followed by utility value and discount rate. CONCLUSIONS:Cost-utility analysis has been widely used in China,but the quality and normalization of studies have much room for improvement. Learning more experiences from international researches can help to promote the quality of domestic studies,guide the practice of clinical rational use of drugs and sup-port the government decision-making process and medical insurance payment in the future.

Comparison and Enlightenment of the Contents of Pharmaceutical Administration in Hospital Accreditation Standards between China and JCI / 中国药房

OBJECTIVE:To provide reference for further refinement and improvement of pharmaceutical administration in hospital accreditation standards in China.METHODS:According to Joint Commission International Accreditation Standards for Hospitals (6th edition) [called "JCI standards (6th edition)" for short] and Implementation Rules of Level 3 General Hospital Accreditation Standards in China (2011 edition) [called "Implementation Rules of Standards (2011 edition)" for short],the similarities and differences of pharmaceutical administration were studied and compared;the advantages and disadvantages of Implementation Rules of Standards (2011 edition) were analyzed to put forward some suggestions on this basis.RESULTS:The number of the items,standards and key points of pharmaceutical administration in JCI standards (6th edition) were 8,22,89,respectively.The number of above indexes in Implementation Rules of Standards(2011 edition) were 11,39,280,respectively.The similarities mainly reflected in relevant laws,regulations,rules and regulations to be followed in pharmaceutical administration,personnel requirements,drug procurement,reserve,storage and recall,drug dispensing and preparation,special drugs management,prescription management,antibiotics management,drug use monitoring,ADR reporting,etc.The specific regulation of JCI standards (6th edition) involved drug management system documentation review,drag acquisition at night or after pharmacy closed,drug list examination,comparison of drug use list before admission and the first medical order,etc.The specific regulation of Implementation Rules of Standards (2011 edition) involved the promotion of National Essential Medicine System and the construction of clinical pharmacist system.CONCLUSIONS:In China,Implementation Rules of Standards (2011 edition) have clearly defined the National Essential Medicine System and the construction of clinical pharmacist system,and are more in line with the development requirements of medical and health services in China at the present stage;but there are also some deficiencies compared to JCI standards (6th edition),including the revision update,the management of the patient's own medicine,the safety management of the patient's identity,measurability of the accreditation standards.Implementation Rules of Standards should be further refined and perfected by updating version regularly,strengthening the management of details,increasing measurability of the accreditation standards,strengthening drug management outside the department of pharmacy,enhancing drug supply management,etc.

Combination of p53 and Rb in the local nano-therapy for rabbit VX2 model of hepatic metastasis ;carcinoma：the curative effect and safety evaluation / 肿瘤研究与临床

Objective Combination of nanoparticle with p53 and Rb gene therapy by gene targeting was applied to investigate its curative effect and safety evaluation on colorectal rabbit hepatic VX2 metastasis for tumor eradication and survival enhancement. Methods Recombinant expressing plasmids harboring wild type p53 and Rb were cotransferred or transferred separately to the rabbit hepatic VX2 metastasis by the emulsion of PLL-nHAP nanoplex and lipodiol through the hepatic artery in a tumor target manner. Subsequent co-expressions of p53 and Rb protein within the treated tumors were detected by Western blot and in situ analysis of confocal laser scanning microscope. The therapeutic effect was evaluated by the tumor growth velocity and the survival time of animals. Eventually, investigations of liver function were applied to evaluate the safety of the process. Results With safe procedure for the rabbits liver function, both p53 and Rb local nano-therapy showed favorable anti-tumor effects and increased animal survival time. p53+Rb local nano-therapy could significantly inhibit hepatic VX2 metastasis and enhance the animal survival time compared with p53 local nano-therapy or Rb local nano-therapy. Local nano-therapy showed no significant influence to animal liver function. Conclusions Rb can work synergistically with p53 in the combined therapy mediated by PLL-nHAP nanoplex to augment the anti-tumor effect. The local nano-therapy with p53 and Rb is likely to be an effective and safe anti-tumor therapy for hepatic colorectal metastasis.

Atorvastatin improves reflow after percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction by decreasing serum uric acid level / 浙江大学学报·医学版

To investigate the effect of atorvastatin on reflow in patients with acute ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) and its relation to serum uric acid levels.One hundred and fourteen STEMI patients undergoing primary PCI were enrolled and randomly divided into two groups:55 cases received oral atorvastatin 20 mg before PCI (routine dose group) and 59 cases received oral atorvastatin 80 mg before PCI (high dose group). According to the initial serum uric acid level, patients in two groups were further divided into normal uric acid subgroup and hyperuricemia subgroup. The changes of uric acid level and coronary artery blood flow after PCI were observed. Correlations between the decrease of uric acid, the dose of atorvastatin and the blood flow of coronary artery after PCI were analyzed.Serum uric acid levels were decreased after treatment in both groups (all<0.05), and patients with hyperuricemia showed more significant decrease in serum uric acid level (<0.05). Compared with the routine dose group, serum uric acid level in patients with hyperuricemia decreased more significantly in the high dose group (<0.05), but no significant difference was observed between patients with normal serum uric acid levels in two groups (>0.05). Among 114 patients, there were 19 cases without reflow after PCI (16.7%). In the routine dose group, there were 12 patients without reflow, in which 3 had normal uric acid and 9 had high uric acid levels (<0.01). In the high dose group, there were 7 patients without reflow, in which 2 had normal uric acid and 5 had high uric acid (<0.05). Logistic regression analysis showed that hyperuricemia was one of independent risk factors for no-reflow after PCI (=1.01, 95%:1.01-1.11,<0.01). The incidence of no-flow after PCI in the routine dose group was 21.8% (12/55), and that in the high dose group was 11.9% (7/59) (<0.01).High dose atorvastatin can decrease serum uric acid levels and improve reflow after PCI in patients with STEMI.

Clinicopathologic characteristics and therapeutic responses of Chinese patients with non-small cell lung cancer who harbor an anaplastic lymphoma kinase rearrangement / 癌症

<p><b>INTRODUCTION</b>The rearrangement of the anaplastic lymphoma kinase (ALK) gene accounts for approximately 1%-6% of lung adenocarcinoma cases and defines a molecular subgroup of tumors characterized by clinical sensitivity to ALK inhibitors such as crizotinib. This study aimed to identify the relationship between ALK rearrangement and the clinicopathologic characteristics of non-small cell lung cancer (NSCLC) and to analyze the therapeutic responses of crizotinib and conventional chemotherapy to ALK rearrangement in NSCLC patients.</p><p><b>METHODS</b>A total of 487 lung cancer patients who underwent testing for ALK rearrangement in our department were included in this study. ALK rearrangement was examined by using fluorescence in situ hybridization (FISH) assay.</p><p><b>RESULTS</b>Among the 487 patients, 44 (9.0%) were diagnosed with ALK rearrangement by using FISH assay. In 123 patients with adenocarcinoma who were non-smokers and of a young age (≤ 58 years old), the frequency of ALK rearrangement was 20.3% (25/123). Short overall survival (OS) was associated with non-adenocarcinoma tumor type (P = 0.006), poorly differentiated tumors (P = 0.001), advanced-stage tumors (P < 0.001), smoking history (P = 0.008), and wild-type epidermal growth factor receptor (EGFR) (P = 0.008). Moreover, patients with poorly differentiated and advanced-stage tumors had a shorter time to cancer progression compared with those with well differentiated (P = 0.023) and early-stage tumors (P = 0.001), respectively.</p><p><b>CONCLUSIONS</b>ALK-rearranged NSCLC tends to occur in younger individuals who are either non-smokers or light smokers with adenocarcinoma. Patients with ALK rearrangement might benefit from ALK inhibitor therapy.</p>

LipoxinA4 reduces lipopolysaccharide-induced expression of cyclooxygenase-2 and prostaglandin E2 in primary lung fibroblasts of rat / 中华急诊医学杂志

Objective To explore the effects of lipoxinA4 on expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in rat primary lung fibroblast cells (LF) after lipopolysaccharide (LPS) challenge.Methods Primary lung fibroblast cells were incubated with various concentrations (0.1,1,10 μg/mL) of LPS for different lengths of time (3,6,9 h).Then primary lung fibroblast cells were still incubated in DMEM medium containing LPS in the presence or absence of lipoxinA4.After incubation,the supematant of medium was collected and the level of PGE2 was detected by using ELISA.The cells were harvested,and COX-2 protein was analyzed by Western blot.Results The model of acute inflammation in fibroblasts was well established by administering 1 μg/mL LPS in fibroblasts for 6 hours.Induction of COX-2 protein by LPS was inhibited by lipoxinA4.The levels of PGE2 in control group,LPS group and LPS + LipoxinA4 group were 55.84 pg/mL,411.73 pg/mL and 307.07 pg/mL,respectively,and there was a significantdifference between LPS group and LPS + LipoxinA4 group (P ＜0.01).Conclusion LipoxinA4 down-regulates the expression of the COX-2 induced by LPS in primary lung fibroblast cells and consequently inhibits the production of PGE2 in a dose dependent manner.