Changes of intestinal flora and the mechanism of NLRP3 inflammasome in elderly mice with cognitive dysfunction induced by sevoflurane anesthesia / 中华行为医学与脑科学杂志

Objective:To investigate changes of intestinal flora and the mechanism of NLRP3 inflammasome in elderly mice with cognitive dysfunction induced by sevoflurane anesthesia.Methods:Eighteen fourteen-month-old male SPF grade C57BL/6J mice were randomly divided into control and sevoflurane groups, with 9 mice in each group. The mice of sevoflurane group inhaled 3% sevoflurane for 2 hours daily for three days. Fecal samples were collected post-exposure 24 hours for 16S rRNA sequencing. Morris water maze was then used to test the cognitive ability. Western blot was used to detect the expressions of synapse-associated proteins, NLRP3 inflammasome-related proteins of hippocampus, and NLRP3 inflammasome-related proteins of colon. Golgi staining was used to observe the number of dendritic spines in the hippocampus. qPCR was used to detect the expression of inflammatory cytokines IL-1β, IL-18, TNF-α mRNA in mice colon and hippocampal tissues.Results:(1) The Morris water maze test showed that the escape latency of the sevoflurane group was longer than the control group, but there was statistical difference only on the fifth day ( P<0.05). In the spatial exploration test, escape latency of the sevoflurane group was higher than that of the control group((49.50±9.99)s, (18.67±7.63)s, t=6.005, P<0.001), and platform crossing frequency was less than that of the control group((0.83±0.75)times, (2.33±1.03)times, t=2.87, P=0.017). (2) Western blot and Golgi staining results showed that the expression of hippocampal synaptic-related proteins and the number of dendritic spines in the sevoflurane group were significantly reduced compared with those in control group (all P<0.05). (3) 16S rRNA sequencing showed significant β-diversity difference between the two groups ( P<0.05). Compared with the control group, potential pathogens that p_Desulfobacterota and g_Desulfovibrio increased significantly in the sevoflurane group (both P<0.05), and beneficial bacteria that p_Verrucomicrobiota and g_Akkermansia decreased significantly (both P<0.05). (4) Compared with the control group, the results of qPCR showed increased expression of inflammatory cytokines TNF-α, IL-1β mRNA in the colon and hippocampal tissues of the sevoflurane group (all P<0.05). Western blot results showed increased expression of NLRP3 inflammasome-related proteins in the colon and hippocampal tissues of the sevoflurane group (both P<0.05). Immunofluorescence results showed the higher fluorescence intensity of ASC in the DG region of the hippocampus of the sevoflurane group compared with the control group ( P<0.01). Conclusion:The cognitive dysfunction model induced by sevoflurane in elderly mice shows neuroinflammatory reactions and synaptic damage, which may be related to intestinal microbiota imbalance and activation of NLRP3 inflammasome.

Literature analysis of leflunomide-induced interstitial pneumonia / 中国药房

OBJECTIVE To study the clinical characteristics of leflunomide-induced int erstitial pneumonia （Lef-IP），and to provide reference for its clinical diagnosis ，treatment and prevention. METHODS Lef-IP cases published in domestic and foreign journals from January 2004 to June 2021 were collected. Relevant information of patients were extracted and analyzed retrospectively， including basic characteristics ，clinical manifestations ，imaging manifestations ，laboratory examinations ， histopathological examinations ，treatment and outcome. RESULTS A total of 54 Lef-IP patients from case reports of 24 publications were included ，with a median age of 61 years（9-83 years）. Pulmonary symptoms appeared from 3.3 weeks to 132.9 weeks（median time of 14.5 weeks）. Patients with a loading dose of leflunomide have a shorter median time to pulmonary symptoms appearing （7.5 weeks）. The main clinical manifestations were dyspnea （85.2％），cough（57.4％），fever（53.7％）. CT imaging examination showed 19 cases with ground-glass shadow in both lungs ，and 29 cases showed interstitial infiltration in both lungs on chest radiograph；blood gas analysis showed hypoxemia and hypocapnia ；the levels of C-reactive protein and Krebs von Den lungen- 6 （KL-6）increased；histopathological examination mainly showed interstitial pneumonia （8 cases），including 3 cases of diffuse alveolar injury ，4 cases of lymphocytes in bronchoalveolar lavage fluid ，and 1 case of noncaseating granuloma. After discontinued leflunomide and symptomatic treatment （antibiotics，hormones，colecenamine，plasma exchange ），35 patients（64.8％）recovered or improved their lung symptoms. Twelve patients （22.2％）died，and patients with fever may had a higher mortality rate （34.5％， P＝0.02）. CONCLUSIONS The main clinical manifestations of Lef-IP are dyspnea ，cough and fever. Loading doses of leflunomide should be avoided at the beginning of treatment. When lef-IP occurs ，leflunomide is discontinued and corresponding treatment is given，and most of the patients ’pulmonary symptoms can return to normal or be improved.

Clinical Features of Neuromyelitis Optica Spectrum Disorders with Connective Tissue Diseases / 中国医学科学院学报

Objective To investigate the clinical features of neuromyelitis optica spectrum disorders(NMOSD)with connective tissue diseases(CTD). Methods Clinical data of 16 NMOSD-CTD patients and 54 NMOSD patients admitted to the Second Affiliated Hospital of Fujian Medical University from January 2015 to February 2020 were collected.The initial symptom,intracranial lesion,spinal cord lesion,laboratory examination and treatment response were compared between the two groups. Results The incidence of Sjögren's syndrome(SS)was the highest(10/16,62.5%)in NMOSD-CTD group.The NMOSD-CTD group had significantly higher positive rate of aquaporin-4 immunoglobulin G(AQP4-IgG)in serum or cerebrospinal fluid(100% vs. 70.2%,P=0.009),higher positive rates of serum anti-nuclear antibodies,anti Sjögren's syndrome A antibodies and anti-Ro52 autoantibodies(P0.05).Conclusions NMOSD is often complicated with CTD,and SS is the most common one.The positive rate of serum or cerebrospinal AQP4-IgG and the seropositivity of several other autoantibodies in NMOSD-CTD patients were higher than those in NMOSD patients.Neurological impairment in NMOSD-CTD patients were severer,which should arouse attention of clinicians.

Angiotensin Type 1 Receptors and Superoxide Anion Production in Hypothalamic Paraventricular Nucleus Contribute to Capsaicin-Induced Excitatory Renal Reflex and Sympathetic Activation / 神经科学通报·英文版

Chemical stimulation of the kidney increases sympathetic activity and blood pressure in rats. The hypothalamic paraventricular nucleus (PVN) is important in mediating the excitatory renal reflex (ERR). In this study, we examined the role of molecular signaling in the PVN in mediating the capsaicin-induced ERR and sympathetic activation. Bilateral PVN microinjections were performed in rats under anesthesia. The ERR was elicited by infusion of capsaicin into the cortico-medullary border of the right kidney. The reflex was evaluated as the capsaicin-induced changes in left renal sympathetic nerve activity and mean arterial pressure. Blockade of angiotensin type 1 receptors with losartan or inhibition of angiotensin-converting enzyme with captopril in the PVN abolished the capsaicin-induced ERR. Renal infusion of capsaicin significantly increased NAD(P)H oxidase activity and superoxide anion production in the PVN, which were prevented by ipsilateral renal denervation or microinjection of losartan into the PVN. Furthermore, either scavenging of superoxide anions or inhibition of NAD(P)H oxidase in the PVN abolished the capsaicin-induced ERR. We conclude that the ERR induced by renal infusion of capsaicin is mediated by angiotensin type 1 receptor-related NAD(P)H oxidase activation and superoxide anion production within the PVN.

Absorptive characteristic of Bletilla striata extract in Caco-2 cell monolayer / 中国中药杂志

To investigate the active fraction from Bletilla striata in Caco-2 cell monolayer,so as to explore its absorption mechanism of oral administration preliminarily.Active fraction from B.striata in Caco-2 cell monolayer was analyzed by UPLC-Q-TOF and detected by UPLC-MS/MS,and the effects of different concentrations,pH and P-glycoprotein inhibitors on Caco-2 cells Monolayer were investigated.Six compounds were isolated from the active fraction of B.striata in Caco-2 cell monolayer by UPLC-Q-TOF,and identified as B6,B12,B14,B17,B19 and B23,with concentration dependence.Within the 0-180 min,the uptake of B12 and B14 had a time dependence,while B6,B17,B19 and B23 tended to saturate after 60 min.All of the components had a good absorption in an acidic environment.B6 had a good absorption at pH 6.0,while the other components B12,B14,B17,B19 and B23 had a good absorption at pH4.0.The absorption of the 6 main components of B.striata were not be affected by P-glycoprotein inhibitors(verapamil/cyclosporin A).Compared with the control group,there was no difference in the absorption of B6 and B12,and the absorption of B14,B17,B19 and B23 increased,but with no significant difference.The absorption characteristic of B.striata extract across the Caco-2 cell monolayer is probably passive diffusion,and the absorption process was not affected by P-glycoprotein.

Application of metabolic network model to analyze intracellular metabolism of industrial microorganisms / 生物工程学报

To quickly and efficiently understand the intracellular metabolic characteristics of industrial microorganisms, and to find potential metabolic engineering targets, genome-scale metabolic network models (GSMMs) as a systems biology tool, are attracting more and more attention. We review here the 20-year history of metabolic network model, analyze the research status and development of GSMMs, summarize the methods for model construction and analysis, and emphasize the applications of metabolic network model for analyzing intracellular metabolic activity of microorganisms from cellular phenotypes, and metabolic engineering. Furthermore, we indicate future development trend of metabolic network model.

Effects of tannins in Galla Chinensis on pharmacokinetics of rifampicin in vivo and in vitro / 中国中药杂志

This study was aimed to explore the effects of tannins in Galla Chinensis on rifampicin in vivo. In the experiment in vitro, UV spectrophotometry and high performance liquid chromatography (HPLC) were used to investigate the solubility of rifampin in pH 1.3, 6.8, artificial gastric juice environment and artificial intestinal fluid environment as well as the effects of tannins on solubility of rifampin in the above conditions. In the experiment in vivo, the process of rifampicin was studied after intragastric administration of rifampicin and rifampicin+ tannins in Galla Chinensis, and then the pharmacokinetic parameters were calculated. The results showed that rifampicin was constantly precipitated in the artificial gastric juice environment over time, and nearly 85% of the rifampicin was precipitated after 6 hours; it showed a good solubility in the artificial intestinal juice environment. After adding the said tannins, the concentration of rifampicin was decreased significantly in both environments, and the concentration of rifampicin in artificial intestinal juice remained relatively stable, while that in artificial gastric juice remained the original downward trend. The pharmacokinetic parameters displayed that as compared with rifampicin alone, AUC0-t and Cmax were decreased significantly, MRT0-t slowed down significantly, Tmax doubled to 7.0 h and the bioavailability was only 31.65% in rifampicin + tannins in Galla Chinensis group. The experiment indicated rifampicin had a poor solubility in acidic environment and the decrease of bioavailability of rifampicin when in combination with tannin was mainly due to the reduction of rifampicin solubility in intestinal tract by complexation of rifampicin with tannin, thus affecting its absorption in intestinal tract. Therefore, rifampicin and the Chinese herbal medicines or Chinese patent medicines rich in tannin should not be taken simultaneously.

The prevalence of hypertension in Keshan disease endemic areas in 2012 in China / 中华地方病学杂志

Objective To investigate the prevalence of hypertension in Keshan disease endemic areas in China,in order to provide evidence for making the policy in hypertension prevention and control for the most disadvantaged people in China.Methods Using non probability sampling method,50 counties with the highest prevalence rate of Keshan disease were selected in the 13 provinces (municipalities and autonomous regions) investigated in the 2012 national monitoring of Keshan disease,and in each county 2 villages were selected as the survey sites.Survey respondents aged over 18 years old were selected as the survey subjects.The prevalence of hypertension in residents was investigated through questionnaire investigation and clinical physical examination.The diagnostic criterion for hypertension was based on the 2010 Chinese Guidelines for the Management of Hypertension.Results A total of 45 165 adults aged 18 years and older were surveyed and 12 329 patients with hypertension in total were found,and the prevalence rate of hypertension was 27.3％.Among which the prevalence of men and women was 27.4％ (5 163/18 868) and 27.3％ (7 166/26 297),respectively.The prevalence rates of hypertension increased with age (x2 =4 132.3,P ＜ 0.05).Among different categories of hypertension,the proportion of grade one hypertension was the largest [33.4％ (4 116/12 329)],and differences between different proportions were significant (x2 =1 586.0,P ＜ 0.05).Conclusions The prevalence of hypertension in Keshan disease endemic areas is significantly higher than the national average level.The prevention and control of hypertension in vulnerable groups in the rural areas and Keshan disease areas should be emphasized.

The prevalence of hypertension in population of Keshan disease endemic areas in China, 2009 / 中华地方病学杂志

Objective To survey the prevalence of hypertension in population of Keshan disease endemic areas, in order to provide a scientific basis for prevention and control of hypertension in rural areas of our country.Methods One hundred and twenty villages were selected as the survey places based on case-finding from 15 provinces including Gansu, Hebei, Henan, Heilongjiang, Jilin, Liaoning, Shaanxi, Shandong, Shanxi, Hubei, Yunnan,Sichuan, Guizhou, Chongqing and Mongolia in 2009.The subjects were permanent residents in the survey places.Basic situation of all subjects was collected through the questionnaire survey and blood pressure was measured by a clinician.Diagnostic criterion for hypertension was based on the Chinese Guidelines for the Management of Hypertension.Results Totally 33 558 subjects aged 18 and over were surveyed, including 8 699 hypertension patients.The positive rate of hypertension was 25.9％ (8 699/33 558), among that 26.3％ (3 532/13 408) were males,and 25.6％ (5 167/20 150) were females.The positive rate of hypertension increased with age (x2 =3 348.325, P ＜0.05).In the classification of hypertension, the proportion of stage 1, 2 and 3 hypertension and isolated systolic hypertension was 31.8％ (2 770/8 699), 26.1％ (2 273/8 699), 17.2％ (1 492/8 699) and 24.9％ (2 164/8 699),respectively.Conclusions The positive rates of hypertension in Keshan disease endemic areas are higher than those of the national average (18.8％).Hypertension is a serious public health problem in Keshan disease endemic areas.The strategy of hypertension prevention and control should be formulated for remote rural areas.

Radiosensitization effect of low-temperature plasma on human malignant cells / 中华放射医学与防护杂志

Objective To evaluate the radiosensitization effect of low-temperature plasma on HepG2, A549, and HeLa cells.Methods Cells were divided into three groups, radiation group (R) , plasma treatment group(P), and plasma plus radiation group (P + R).After radiation, cell survival was detected by a cloning assay.Cell cycle distribution, apoptosis and ROS content were tested by flow cytometry.Western blot was used to measure the expressions of Caspase-3 and Bcl-2.Results Lowtemperature plasma showed radiosensitization effects on three different human malignant cell lines with a sensitivity enhancement ratio(SERD0) of 1.28,1.32 and 1.29.respectively.In these three different human malignant cell lines, compared with radiation alone group (R) , the G2/M arrest, apoptosis rate and ROS level in the group P + R were enhanced (the prolongation of G2/M arrest: t =9.52, 8.24, 9.53, P ＜ 0.05;the apoptosis rate: t =10.67, 38.56, 6.74, P ＜0.05;ROS content: t =9.41, 15.42, 13.53, P ＜0.05).In HepG2 cells and A549 cells, compared with group P, the prolongation of G2/M arrest, the apoptosis rate and ROS content of group P + R were enhanced (the prolongation of G2/M arrest: t =8.75, 20.37, P＜0.05;the apoptosis rate: t =8.43, 9.99, P ＜0.05;ROS content: t =4.82, 5.27, P ＜ 0.05).The expression level of Bcl-2 protein was downregulated in group P + R;by contrast, the expression level of Caspase-3 protein in group P + R was upregulated.Conclusions Low-temperature plasma can increase the radiosensitization of HepG2, A549 and HeLa cells with the enhancement of G2/M phase arrest, apoptosis induction and ROS generation.

Histology research on repairing of rabbit articular cartilage defects with naringin and tissue engineering cartilage / 中国组织工程研究

BACKGROUND:At present, there are many methods to treat cartilage defects, but none radical y repairs the articular cartilage defects. OBJECTIVE:To histological y verify the effect of naringin combined with tissue engineering cartilage on the repair of rabbit articular cartilage defects. METHODS:Rabbit bone marrow mesenchymal stem cells fol owing in vitro proliferation were compounded onto acellular dermal matrix, which was then implanted into rabbit knee cartilage defects. Naringin was also given by lavage. Hematoxylin-eosin staining, Masson trichrome staining, toluidine blue dyeing, type II col agen staining and type X col agen staining were performed in the repaired tissue. RESULTS AND CONCLUSION:After 8 weeks post-surgery, the defects repaired with the naringin and stem cells composite were turned into milky-white and transparent smooth tissue. The defective tissue which was repaired, was very similar to normal cartilage tissue, with smooth surface. After the histology research, we found that the defect tissue was fil ed with new cartilage tissue. Results indicated that naringin combined with tissue engineering cartilage can promote the repair of articular cartilage defects in rabbits.

Cleaning the surveillance data of Keshan disease in 2009, China / 中华地方病学杂志

Objective To investigate potential problems and solutions within the data of national surveillance of Keshan disease(KSD), to improve the quality of surveillance data and the reliability of the results. Methods Four key variables (name, sex, age, and KSD diagnosis) in the national surveillance data of KSD in 2009 were cleaned by SPSS 15.0. Cleaning contents included duplicate records, missing values, outliers and logic errors. Name, sex, age, currently residing in townships and currently residing in villages and other variables were combined into different filters to find duplicate records by the command of Identify Duplicate Cases , then the duplicate records were returned to the data reporting agencies, and finally delete or merge. Data with missing values, outliers, or logical errors were found by commands of Frequencies, Descriptives and Select if, then the duplicate records were returned to the data reporting agencies. Data were revised based on not only the feedback , but also by using the relationship between variables, and by consulting KSD clinical experts. Results Four hundred and sixty-four cases of duplicate records were found and cleaned. The number of missing values was 2 047 (specifically, name 0, sex 3, age 32 and KSD diagnosis 2 012). The number of outliers was 1 988 (specifically, name 6, sex 3, age 10 and KSD diagnosis 1 969). The records of 5 kinds of logic errors of KSD diagnosis were 105 in all. Conclusion There are duplicate records, missing values, outliers and logic errors in the national surveillance data of KSD, cleaning work could improve the quality of surveillance data, ensure the authenticity and rliability of the monitoring data.

Biomechanical comparison of Evans procedure and Chrisman-Snook technique for the treatment of II degree lateral collateral ligament of ankle joint / 中国骨伤

<p><b>OBJECTIVE</b>To measure the stability of Evans procedure and Chrisman-Snook technique in the treatment of II degree lateral collateral ligament of ankle joint, and provide basis for treatment and prognosis.</p><p><b>METHODS</b>From July 2008 to June 2009,18 frozen corpes were collected, including 10 males and 8 females, with an average age of fresh 39.3 +/- 11.2 years. The frozen corpes were randomly divided into three group, including normal controls(group A), Evans procedure (group B) and Chrisman-Snook technique ( group C), 6 specimens in each group. Anterior talofibular ligament and calcaneofibular ligament were cut off to cause II degree lateral collateral ligament in group B and C. Evans procedure or Chrisman-Snook technique were applied to restore lateral collateral ligament, and measure biomechnics. The displacement of tibiotalar joint and subtalar joint were observed.</p><p><b>RESULTS</b>(1) The lateral stress results of tibiotalar joint showed the displacement by Evans procedure (group B) was greater than other groups (P < 0.0001). There were no significant differences between group A and C (P > 0.05). (2) The lateral stress results of subtalar joint showed the displacement by Evans procedure (group B) was greater than other groups (P< 0.0001). There were no significant differences between group A and C (P > 0.05).</p><p><b>CONCLUSION</b>Ankle instability is caused by ankle joint lateral collateral ligament injury. Chrisman-Snook technique is better than Evans procedure in stability on the early stage of ankle joint restoration, and conform to principle of biomechanics.</p>

Maxillary sinus floor augmentation using gene-enhanced tissue engineered bone / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of maxillary sinus elevation with gene-enhanced tissue engineering bone in dogs.</p><p><b>METHODS</b>bone marrow stromal cells (BMSC) derived from dog marrow were cultured, and transduced with the adenovirus carrying bone morphogenetic protein-2 (BMP-2) gene (AdBMP-2), the adenovirus carrying green fluorescent protein (GFP) gene (AdGFP) in vitro. The bone formation ability of gene modified BMSC with scaffold was examined in nude mice and in elevated maxillary sinus of dog. Student's t-test was used for statistical analysis with SPSS 11.0 software package.</p><p><b>RESULTS</b>Gene transfection efficiency reached up to (83.95 ± 2.43)% as demonstrated by GFP expression. Ectopic bone formation was detected in nude mice. As for maxillary sinus floor elevation in a dog model, new bone formation area in the AdBMP-2 gene transduced BMSC with Bio-Oss group was significantly higher than in BMSC with Bio-Oss group at 120 d (P < 0.05).</p><p><b>CONCLUSIONS</b>AdBMP-2 gene transduced BMSC can stimulate ectopic bone formation in nude mice, and promote bone formation and maturation in the dog maxillary sinus.</p>

The changes and clinical significance of the frequency of CD4+ CD25+ regulatory T cells in the peripheral blood of patients with nonalcoholic fatty liver / 中华传染病杂志

Objective To investigate the changes and clinical significance of the frequency of circulating CD4+ CD25+ regulatory T cells (Treg) in nonalcoholic fatty liver (NAFL) patients.Methods CD4+ CD25+ Treg in the peripheral blood from 50 NAFL patients and 50 healthy subjects were quantitatively analyzed using flow cytometry. Group t test or Mann-Whitney U test and Spearman's rank correlation test were used for statistical analysis.Results The proportion of circulating CD4+CD25+ Treg in NAFL patients was (5.39 ± 1.94)％,which was significantly higher than that in healthy controls [(4.21±1.52)％](t=3.385,P＜0.01).Further analysis revealed that the frequency of Treg was positively correlated with triglyceride (TG) level and body mass index (r=0.307 and 0.251,respectively; P=0.002 and 0.012,respectively),and negatively correlated with high density lipoproteincholesterol (HDL-C) (r=-0.306,P=0.002).Meanwhile,Treg in patients with high body mass index,high TG,low HDL-C,hypertension and metabolic syndrome (MS) were all higher than those in controls (t=2.294,2.533,3.154,2.010 and 4.454,respectively; all P＜0.05).But there was no significant difference between patients with high fasting blood glucose and controls (U=1143.500,P=0.471).Conclusion The increased frequency of peripheral Treg in NAFL patients may have some relations with the imbalance of proinflammation and anti-inflammation in NAFL patients who coexisting with MS.

Dynamic expressions and the significance of Notch/Jagged signal pathway in rat model of hepatic fibrosis / 中华传染病杂志

Objective To explore the dynamic expressions and the significance of Notch/Jagged signal pathway in rat model of hepatic fibrosis. Methods A total of 42 healthy male SD rats were randomly divided into normal control group (n=6) and model group (n= 36). The model group was further divided into six subgroup according to different time points: subgroups of 4 days, 1, 2, 4, 6 and 8 weeks with six rats in each subgroup. The rat model of hepatic fibrosis was induced by dimethylnitrosamine (DMN). The serum levels of alanine aminotransferase (ALT), aspertate aminotransferase (AST), albumin (Alb) and hyaluronic acid (HA) were detected dynamically after 4 days, 1,2,4,6 and 8 weeks of injection. The liver tissues were observed under optical microscope after HE and Masson staining. Notch-1, Jagged-1 mRNA and protein in liver were detected by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. The comparison of means among groups was done by univariate ANOVA. Results The hepatic fibrosis model was successfully induced by DMN injection and pseudolobules were found after 4 weeks of injection. The serum levels of ALT, AST, Alb and HA were all increased after 4 day of injection and peaked at week 4 which were all significantly higher than those in control group (F=83.10, 104.63, 54.24, 203.81,respectively; all P＜0.05). The expressions of Notch-1, Jagged-1 mRNA and protein in model group were all significantly increased than those in control group (F=282. 44, 369.14, 374.17, 256. 14,respectively;P＜0. 01). And the expressions of Notch-1, Jagged-1 were closely correlated with the hepatic fibrosis stages and transforming growth factor β1 (TGFβ1) expression (r=0. 821, 0. 917,0. 767,0. 844, respectively; P＜0. 01 ). Conclusions The Notch/Jagged pathway may participate in the development of hepatic fibrosis, which is closely correlated with the progression and severity of liver fibrosis.

Dynamic expressions of exchange protein directly activated by cyclic adenosine monophosphate in rat model of liver fibrosis / 中华传染病杂志

Objective To investigate the dynamic expressions of exchange protein directly activated by cyclic adenosine monophosphate (cAMP) (Epac) in rat model of hepatic fibrosis(HF).Methods Forty-two male SD rats were divided into control group (n = 6) and model group (n = 36)which was divided into six subgroups of day 4, week 1, week 2, week 4,week 6 and week 8 with six rats in each subgroup. The rat model of HF was established by intraperitoneal injection of dimethylnitrosamine (DMN). The pathological changes of liver were observed by Hematoxylin-Eosin and Masson staining. Reverse transcription-polymerase chain reaction (RT-PCR),immunohistochemistry and Western blot were employed to detect the mRNA and protein expressions of Epac1, Epac2 and transforming gronth factor (TGF)β1 during the process of modeling and localization in the liver. The statistical analysis was done using one-factor ANOVA, LSD-t test,Dunnett T3 test and Pearson linear correlation analysis. Results Rat model of liver fibrosis was established successfully. In control group, Epac1 (0. 031 28±0. 008 96) and Epac2 protein (0.034 43±0. 002 45) mainly expressed in the cytoplasm of hepatocytes. In model group, the level of Epac1 decreased at day 4 (0. 023 97±0. 003 81) and week 1 (0. 015 81±0. 002 48) ,then began to increase at week 2 of modeling and peaked at week 6 (0. 039 54±0. 001 43), which had statistical significance compared to the control group (t= 5.47,11.58 and - 6.18, respectively; all P＜0.05). Epac2 protein expression declined after modeling, reached the lowest level at week 4 (0. 011 21 ±0. 001 32), which had statistical significance compared to the control group (t= 24. 50, P＜0. 05). TGFβ1 protein expression increased after modeling and peaked at week 4 (0. 011 30±0.001 03) which had statistical significance (t= -23. 36, P＜0. 05) compared to the control group (0. 002 08 ±0. 000 18). The expressions of Epac1, Epac2 and TGFβ1 mRNA were consistent with the trend of protein levels.Correlation analysis showed that Epac1 protein was positively correlated with the course of HF (r =0. 703, P＜0.01 ), while Epac2 protein was negatively correlated (r = - 0. 409, P＜0.05). Conclusions During the progression of HF, Epac1 expression tends to decrease firstly and increase afterwards,while Epac2 expression declines continually. Epac may be involved in the pathogenesis of HF.

Dynamic expressions of interleukin-1 receptor associated kinase-4 and interleukin-1 receptor associated kinase-M in rats with endotoxin tolerance and their significance / 中华传染病杂志

Objective To explore the dynamic expressions of interleukin-1 (IL-1)receptor associated kinase (IRAK)-M and IRAK-4 in rats with or without endotoxin tolerance (ETT)in acute liver failure (ALF).Methods Sixty-six male SD rats were divided into three groups:ALF group,ETT group and control group.The rats in ETT group received daily lipopolysaccharide (LPS)intraperitoneal injection for 5 days,while the rats in ALF group received daily injection with same volume of 0.75% NaCl solution.Both ETT group and ALF group received intraperitoneal injection with D-galactosamine (D-GalN)and LPS at 24 hours after the 5th injection of LPS or NaCl solution.At 2,6,12,24 and 48 h after D-GalN and LPS injection,the serum levels of tumor necrosis factor-α (TNF-α)and interleukin-6 (IL-6)were detected by enzyme-linked immunosorbent assay (ELISA).The liver pathologic changes were observed with HE staining by microscope.The mRNA expressions of IRAK-4,IRAK-M and NF-κB (p65)were detected by reverse transcriptase polymerase chain reaction (RT-PCR).The pairwise comparison between groups was done by lease significant difference (LSD)and Dunnet's t test.Results The liver pathologic changes in ETT group were much milder than those of ALF group.In ALF group,IRAK-4 mRNA/β-actin absorbance ratios at 2,6,12,24and 48 h after D-GalN and LPS challenge were 0.711 ±0.074,0.904±0.118,1.012 ±0.098,1.534±0.279 and 1.451±0.290,respectively,while the IRAK-M mRNA/β-actin absorbance ratios were 0.496±0.018,0.516±0.089,0.503±0.023,0.503±0.057 and 0.469±0.142,respectively.In ETT group,the IRAK-4 mRNA/β-actin absorbance ratios at 2,6,12,24 and 48 h after D-GalN and LPS challenge were 0.619±0.083,0.587±0.033,0.623±0.034,0.720±0.044 and 0.654±0.041,respectively,while the IRA'K-M mRNA/β-actin absorbance ratios were 0.929 ± 0.064,1.111±0.138,1.113±0.027,1.891±0.315 and 1.710±0.303,respectively.The IRAK-M mRNA expression level was significantly increased and IRAK-4 mRNA expression level was relatively decreased in ETT group compared to ALF group.The differences were all statistically significant at 2,6,12,24 and 48 h after D-GalN and LPS challenge (F= 17.305,54.921,121.031,67.607,55.279,respectively; F=19.506,43.777,110.823,302.681,202.822,respectively; F=172.003,59.519,987.055,68.463,96.601,respectively; all P＜0.05).Conclusion LPS pretreatment may induce ETT in rat model by downregulating the expression of IRAK-4 and upregulating the expression of IRAK-M.

Comparison of five scoring systems for predicting the prognosis of patients with chronic severe hepatitis / 中华传染病杂志

Objective To investigate the roles of five scoring systems including model for endstage liver disease (MELD), Child-Turcotte-Pugh (CTP), Mayo, MESO and MELD-Na scoring systems, in predicting the prognosis of patients with chronic severe hepatitis. Methods The clinical data of 213 patients with chronic severe hepatitis were retrospectively studied. The five scoring systems were applied respectively to evaluate the scores in survival group and death group. The capability of these five scoring systems to predict the prognosis of severe hepatitis were compared by the receiver operating characteristic (ROC) curve, area under curve (AUC) and cut-off value.Measurement data were compared by group t test. The comparisons of AUC among scoring systems were done using MEDCLAC software. Results The scores of death group evaluated by MELD, CTP,Mayo, MESO or MELD-Na scoring systems (30.6 ± 9.5, 11.3 ± 1.5, 10.4 ± 1.3, 2.3 ± 0.8 and 39.0 ± 11.8, respectively) were consistently higher than those of survival group (21.1± 6.8, 10.6 ±1.6, 9.0±1.5, 1.6±0.5 and 22.6±8.2, respectively) (P＜0.01). The values of AUC of these five systems were 0.810, 0.623, 0.749, 0.829 and 0.885, respectively. The Youden's indexes of these five systems were 0.507, 0.175, 0.389, 0.528 and 0.650, respectively. Conclusions The CTP scoring systems can not predict the prognosis of chronic severe hepatitis very well. The Mayo scoring systems can partially predict the prognosis. On the contrary, MELD, MESO and MELD-Na systems can successfully predict the disease prognosis, and the score of MELD-Na system shows the best correlation with the prognosis.

Cervical diffusion tensor imaging for diagnosis of amyotrophic lateral sclerosis / 中华神经医学杂志

Objective To investigate the application of cervical diffusion tensor imaging (DTI) in the diagnosis of amyotrophic lateral sclerosis (ALS). Methods Cervical DTI and conventional magnetic resonance imaging (MRI) was performed in 28 ALS patients rated with ALS functional rating scale (ALSFRS) and 20 healthy control subjects to obtain the mean diffusivity (MD) and fractional anisotropy (FA) histograms of the cervical spinal cord. Correlation analysis between DTI of the cervical spinal cord and the ALSFRS scores of the ALS patients was conducted. Results Compared with the control subjects, the ALS patients had significantly lowered mean FA and reduced cross-sectional area of the cervical spinal cord (P<0.05), but the MD value did not differ significantly between the two groups (P>0.05). A close correlation was found between the mean FA of the cervical spinal cord and the ALSFRS score (r=0.730,P=0.000), but not between the MD value and the ALSFRS score in the ALS patients. Conclusion Patients with ALS have significantly lowered mean FA, which may serve as an indicator for the diagnosis orALS. Together with the ALSFRS score, cervical DTI can better characterize the progression of ALS.