AIM: To study the effect of cGMP-dependent protein kinase (PKG) on the pathogenesis of burn shock. METHODS: Confluent endothelial cells were disintegrated and centrifugated to obtain cell lysates after being treated with 10% burn serum or PKG activator 8-Br-cGMP. PKG activity of lysates was measured with radioactive isotope label method in a reaction system of phosphorylation of specific substrate H2B by PKG, and the shape and the distribution of intracellular filamentous actin were detected by specific fluorescence staining. For the control study, the PKG specific inhibitor KT5823 were used to pretreat the endothelial cells before the administration of burn serum or PKG activator 8-Br-cGMP. RESULTS: Exposures to burn serum and 8-Br-cGMP led to a rapid time-dependent increase in endothelial PKG activity and the polar distribution of intracellular filamentous actin, and preincubation with KT5823 abolished those effects. CONCLUSIONS: The results suggest that burn serum induces PKG activation and the stress variety of filamentous actin in the vascular endothelial cells, which probably contributes to the endothelial hyperpermeability after burn shock. [

BACKGROUND:Recent studies have suggested that intranasal administration is one of the ways to target drugdelivery, and can effectively make the drug that cannot pass through the blood brain barrier by other pathways to bypass the blood brain barrier, resulting in targeted delivery to the brain. It provides a promising route for the treatment of central nervous system diseases. OBJECTIVE: To study the pharmacokinetic and brain-targeted channel-tropism tissue distribution character of cimicifugoside H-1 after nasal and intravenous administration in plasma and tissues in rats, in order to evaluate the feasibility of developing brain-targeted nasal delivery system of cimicifugoside H-1 by the passage between nose and brain in nasal olfactory area. METHODS: After intravenous injection and nasal administration of cimicifugoside H-1, the drug concentrations of plasma and channel-tropism organs (lung, spleen, stomach, large intestine, liver, kidney, brain, brain, cerebelum, cerebrospinal fluid, olfactory bulb and olfactory region) were detected. Drug-time curve was drawn. DAS program was used to select apartment model and pharmacokinetics parameters. RESULTS AND CONCLUSION:(1) The pharmacokinetics characters of cimicifugoside H-1 are rapidly absorbed and extensively distribution. Among major channel-tropism organs, drug concentrations were higher in the lung and brain than in the other organs. (2) Cimicifugoside H-1 could be straightly transported into brain by the intranasal administration. The molecule through olfactory mucosa in nasal cavity entered into olfactory bulb in arachno-hypostegal cavity, and then entered into olfactory region, cerebrospinal fluid, cerebrum and cerebelum gradualy. Olfactory bulb was the only way for drug molecule to go through nasal cavity into brain. (3) Compared with the intravenous injection, cimicifugoside H-1 through the intranasal administration has a significant

Objective To study the Janus Kinase 2 V617F (JAK2V617F) point mutation in bcr-abl-negative myeloproliferative disorders (MPD) and explore its clinical significances. Methods Genomic DNA was isolated from bone marrow or peripheral-blood granulocytes. Allelespecific-polymerase chain reactions (AS-PCR), restriction enzyme digestion in combination with PCR product sequencing were performed to detect the mutation in genomic DNA. 110 patients were detected, including 41 with bcr-ablnegative MPD, 25 with bcr-abl-positive chronic myelogenous leukemia (CML), and 44 with acute leukemia.Results JAK2V617F was presented in 11 cases(91.7 %) of 12 polycythemia vera (PV), 8 cases(53.3 %) of 15 essential thrombocythemia(ET), 4 cases (57.1%) of 7 idiopathic myelofibrosis (IMF), while in other patients including 7 hypereosinophilic syndrome (HES), 25 bcr-abl-positive CML, 24 acute myelocytic leukemia (AML), 18 acute lymphoblastic leukemia(ALL), and 2 acute mixed lineage leukemia, JAK2V617F can not be detected. All positive samples and 10 negative samples identified by AS-PCR and restriction enzyme digestion were confirmed further by DNA sequencing. Conclusion The frequency of JAK2V617F mutation was more than 90 % among patients with PV, more than 50 % among patients with ET and IMF. The detection of JAK2V617F mutation will be of great significanees in the diagnosis and differential diagnosis of MPD. This mutation can be a molecular marker of MPD and might be a treatment target in the future.

BACKGROUND:Previous study has confirmed that seasonal variation and surfactant associated protein A(SP-A)and interleukin-6(IL-6)exhibit a significant role in lung immune and defense function.However,the effect mechanism of them remains unclear.OBJECTIVE:By observing the changes of SP-A and IL-6 of male rats in autumn and winter.to explore the effects of seasonal changes on the nonspecific immunity of lung of normal rats,and to provide new ideas for the experimental basis to the cognition of pathology and physiology mechanism for seasonal attack of respiratory system diseases.METHODS:Male SD rats were purchased from each seasons and divided into groups in chronological order All rats were housed with normal forage and drank freely under room temperature.Then the rats were sacrificed by decapitation before 18 o'clock at corresponding solar term and the lung tissues were analyzed by RT-PCR.RESULTS AND CONCLUSION:Compared to the other groups.the expression of SP-A and IL-6 in the Winter Begins group were smaller.which demonstrated that immune function of lung was existed the seasonaI rhythm of lower in winter and higher in autumn.The SP-A and IL-6 are main material basis of immune function.

Objective To use metabonomics method to study the change of the basic materials of month rhythm of wei qi deficiency syndrome; To find the potential markers so as to provides a new way for the essence of the wei qi deficiency syndrome research.Methods Based on the autumnal equinox in lunar calendar month, the beginning of a month (the first day of lunar August), the middle of a month (the 15th day of lunar August), and the end of a month (the 30th day of lunar August) were set as the three days to draw experimental materials. Two weeks before drawing materials, 20 rats were randomly divided into control group and model group, 10 rats in each group. The model rats were modeled by the stimulus of fatigue combined with coldness and hotness. Control group rats received conventional breeding. The rats in the both groups during the three experiments received decollation and the blood was taken at the 12 o’clock at noon. HPLC-MS was used to detect plasma metabolites, and partial least squares were used to make statistical analysis on the data for comparing plasma metabonomics original data of control group and model group. Possible metabolic markers of wei qi deficiency syndrome were explored, and the potential makers of month rhythm change of wei qi deficiency syndrome were deduced.Results Oleamide, phosphatidyl glycerol, cortisol, proline, dimethyl fumarate, and eicosapentaenoic acid may be potential markers of wei qi deficiency syndrome in the beginning of a month. Sphingosine-1-phosphate, malic acid, cortisol, oleamide, carnitine, eicosapentaenoic acid and dimethyl fumarate may be potential markers of wei qi deficiency syndrome in the middle of a month. Cholesteryl acetate, threonine, cortisol, dimethyl fumarate, oleamide, eicosapentaenoic acid and pyroglutamate may be potential markers of wei qi deficiency syndrome in the end of a month.Conclusion Month rhythm change of wei qi deficiency syndrome may be influenced by oleamide, cortisol, eicosapentaenoic acid, dimethyl fumarate, and aconitic acid, and may be closely related to energy metabolism, meanwhile accompanied by regulation of cell, hormone and nerves.

Klebsiella pneumoniae liver abscess accompanied by metastatic infectious complications was firstly reported in 1986. The pathogen was defined as Hypervirulent K. pneumoniae (hvKp) after a series of studies, which is an evolving pathotype and more virulent than classical K. pneumoniae (cKp). At present, it is difficult to distinguish hvKp and cKp in the clinical microbiology lab, which results in delay in early diagnosis and treatment on hvKp-related infections. Biliary tract diseases after cholangiojejunostomy, biliary interventional therapy and liver transplantation have become common causes of recurrent acute cholangitis. The incidence of bacterial liver abscess is on the rise, especially the infection caused by multidrug-resistant bacteria. This article reviews difficulties in the diagnosis and treatment of bacterial liver abscess.

Objective: To investigate the value of NPM1 and FLT3 gene mutation combined with bone marrow imaging detection in the prognosis judgement of initial treatment cytogenetically normal acute myeloid leukemia (CN-AML). Methods: The clinical data of 100 patients (non-M₃ type) with primary and initial treatment CN-AML from January 2010 to January 2014 in the Peace Hospital Affiliated of Changzhi Medical College were retrospectively analyzed. All patients were enrolled in the bone marrow imaging examination on the end day of induction treatment or the first day after the end of induction treatment (T time point). Univariate and multivariate prognostic analyses were performed on AML patients according to FLT3 and NPM1 gene status,bone marrow juvenile cell ratio at T time point. Results: A total of 100 patients included 36 cases with FLT3 gene mutation and 44 cases with NPM1 gene mutation. The complete remission (CR) rate of CN-AML patients was 13.9% (5/36) and 71.9% (46/64), respectively (P < 0.01), 2-year recurrence-free survival (RFS) rate was 5.6% and 59.8%, respectively (P < 0.01), 2-year overall survival (OS) rate was 15.6% and 66.2%, respectively in FLT3⁺ group and FLT3^- group (P < 0.01). The median RFS and median OS time in FLT3⁺ group was 6.9 months and 9.4 months, respectively, and the median RFS and median OS time in FLT3^- group had not yet reached. There were no significant differences of all the indexes between the two groups (all P < 0.01). And there were no significant differences in CR rate, 2-year RFS rate and 2-year OS rate between NPM1⁺ group and NPM1^- group (all P > 0.05). The CR rate, 2-year RFS rate and 2-year OS rate in NPM1⁺ FLT3^- group were better than those in NPM1^- FLT3^-, NPM1^- FLT3⁺ and NPM1⁺ FLT3⁺ groups; NPM1^- FLT3⁺ and NPM1⁺ FLT3⁺ groups had the worst prognosis, and there were no statistical differences in the CR rate, RFS and OS time between the two groups (all P > 0.05). The prognosis of the patients in bone marrow juvenile cell ratio < 0.05 group at T time point was better than that in ratio ≥0.05 group (all P < 0.05). CN-AML patients were classified into the good prognosis group (NPM1^- FLT3^-), the medium prognosis group (NPM1⁺ FLT3^-), and the poor prognosis group (NPM1^- FLT3⁺ and NPM1⁺ FLT3⁺) according to the FLT3 and NPM1 genes. The good prognosis group+ the ratio of bone marrow juvenile cells at T time point < 0.05 group, the good prognosis group+ the ratio of bone marrow juvenile cells at T time point ≥0.05 group, the medium prognosis group+ the ratio of bone marrow juvenile cells at T time point < 0.05 group had no statistical differences in CR rate, 2-year RFS rate and 2-year OS rate (all P > 0.05). The medium prognosis group+ the ratio of bone marrow juvenile cells at T time point ≥0.05 group, the poor prognosis group+ the ratio of bone marrow juvenile cells at T time point < 0.05 group had the equivalent prognosis, and the average prognosis was moderate; the poor prognosis group+ the ratio of bone marrow juvenile cells at T time point ≥ 0.05 group had the worst prognosis. According to Cox multivariate regression analysis, FLT3 gene mutation and the ratio of bone marrow juvenile cells at T time point were independent influencing factors for RFS and OS in CN-AML patients (all P < 0.05). NPM1 was an independent prognosis factor affecting RFS and OS of FLT3^- patients (all P < 0.05). Conclusions After induction chemotherapy, the responsiveness and sensitivity of AML patients to chemotherapy regimen can be assessed early and objectively according to molecular genetics and the ratio of bone marrow juvenile cells at T time point, which has a certain value in the prognosis judgement.

Objective: To explore the relationship between sleep problems and non-suicidal self-injury behavior in Chinese college students, and to provide scientific basis for the prevention and intervention of non-suicidal self-injury behavior. Methods: A cross-sectional survey of 11 689 college students from three universities in Guangzhou were selected as the research subjects. A questionnaire survey of college students’ mental health was conducted to investigate non-suicidal self-injury behavior, sleep problems, demographic information, lifestyle, and depressive symptoms. Results: In the past year, the prevalence rates of non-suicidal self-injury in college students was 7.8%. Univariate Logistic analysis showed that all sleep problems were associated with non-suicidal self-injury behavior(P<0.05). After controlling for potential confounders,including grade,gender,parents’ education level,health conditon,family income,smoking,drinking and depression,multivariate Logistic regression showed that shorter sleep time at weekend (<7 h/d), insomnia symptoms and frequent nightmares significantly increased the risk of nonsuicidal selfinjury behavior in college students (OR=1.32-3.25, P<0.05), while longer sleep time at weekdays (≥9 h/d) was an important protective factor (OR=0.60, P<0.05). Conclusion These findings indicate that short sleep time, insomnia and nightmares are important risk factors for college students’ non-suicidal self-injury behavior. Intervention and management on sleep problems can effectively reduce the occurrence of self-injury behaviors.

Objective:To seek specific response points on the body surface of patients with primary dysmenorrhea(PD)by observing blood perfusion unit(PU)at different points of the three Yin meridians of foot using laser speckle contrast imaging(LSCI). Methods:Eighty PD patients were recruited as a PD group,and 80 healthy female undergraduates were taken as a normal group.During one menstrual cycle(before menstruation,during menstruation,and 3 d after menstruation),each participant was examined using the LSCI system to determine PU at bilateral Taixi(KI3),Taibai(SP3),Taichong(LR3),Shuiquan(KI5),Diji(SP8),Zhongdu(LR6),Sanyinjiao(SP6),and Xuehai(SP10)and non-acupuncture points.The researchers in charge of point location,operation,and statistical analysis were not aware of grouping.PU at the detection spots was taken as the outcome measure. Results:Compared with the normal group,the PD group showed increases in PU at right Taixi(KI3)before menstruation(P<0.05)and at bilateral Zhongdu(LR6)and right Diji(SP8)during menstruation(P<0.05).At the other time points,significance was not found between the two groups in comparing PU at the detected spots. Conclusion:Compared with healthy participants,PD patients present specific changes in PU at Taixi(KI3),Diji(SP8),and Zhongdu(LR6)at specific time points during the menstrual cycle,which provides a reference for acupuncture-moxibustion treatment of PD in clinical settings.

Objective:To analyze the clinical characteristics and risk stratification of 182 patients with acute pulmonary embolism (APE), and to investigate the correlation of neutrophil (N)/lymphocyte (L) ratio (NLR) and risk stratification/prognosis.Methods:The clinical data of 182 APE patients admitted to Peking University People’s Hospital from January 2015 to March 2021 were retrospectively collected, including age, sex, symptoms and signs, blood pressure, blood gas analysis, blood routine parameters, cardiac biomarkers, coagulation parameters, and right ventricular imaging parameters. The patients were divided into groups according to the risk stratification at admission and prognosis in hospital. χ2 test, t test or nonparametric test were used to analyze the differences in clinical characteristics, blood routine parameters, blood gas analysis, coagulation parameters and other parameters between the groups. Multivariate logistic regression analysis was used to study the independent risk factors for the prognosis of APE. Results:Among the 182 patients, 79 were male and 103 were female, 23 were in the high-risk group, 51 were in the intermediate-high-risk group, 46 were in the intermediate-low risk group, and 62 were in the low-risk group. There were 27 deaths and 155 survivors. The respiratory rate of the high/intermediate-high-risk group was significantly higher than that of the low/intermediate-low-risk group. Compared with the other three groups, pH, oxygen partial pressure (PO 2) and blood oxygen saturation (SO 2) in the high-risk group were significantly lower ( both P<0.05). There were statistically significant differences in WBC, N, and NLR levels between the high/intermediate-high-risk group and low/intermediate-low-risk group ( both P<0.05). However there were no significant differences in PLT, PLT/MPV, PLT/PDW, and coagulation related parameters PT, FIB, APTT and D-D between groups (all P > 0.05). MPV and PDW were only significantly different between the low-risk group, intermediate-low-risk group and high-risk group ( both P<0.05). Multivariate logistic regression analysis showed that NLR ( OR=1.179,95% CI:1.029-1.410, P=0.039) and PH ( OR=1.156,95% CI:1.031-1.522, P=0.041) were independent predictors of in-hospital mortality. The ROC curve was used to analyze the predictive value of NLR for in-hospital mortality. When the cutoff value of NLR was 8.38, the AUC of NLR was 0.824 (95% CI: 0.829-0.913), the corresponding sensitivity was 0.831, and the specificity was 0.887. Conclusions:NLR is correlated with risk stratification and prognosis of APE, and is an independent risk factor for poor prognosis.