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Objective:To observe aqueous cytomegalovirus (CMV) DNA load in patients with cytomegalovirus retinitis (CMVR) after allogeneic hematopoietic stem cell transplantation (Allo-HSCT), and to explore influencing factors for transient elevation of CMV-DNA load during the treatment.Methods:A retrospective study. From January 2016 to July 2020, 28 eyes of 19 patients with CMVR after Allo-HSCT diagnosed in the Department of Ophthalmology of Peking University People's Hospital were included in the study. Among them, there were 8 males with 12 eyes, 11 females with 16 eyes; the mean age was 28 years; 10 patients were unilateral and 9 patients were bilateral. During the course of treatment and follow-up, the blood CMV-DNA remained negative. All patients were treated with intravitreal injection of 60 mg/ml ganciclovir 0.05 ml (containing ganciclovir 3 mg), twice a week for two weeks in induction phase and weekly injection in maintenance phase. Aqueous humor sample was collected during injection of ganciclovir (IVG) and CMV-DNA load was determined by real-time quantitative polymerase chain reaction. Intravitreal treatment was terminated if aqueous CMV-DNA load turned negative after the fourth or later intravitreal injection. The patients were followed up every 2 weeks for at least 6 months. Serum CMV-DNA was negative in all patients during treatment and follow-up. All the eyes were divided into continuous decline group and non-continuous decline group depending on whether there was transient elevation of aqueous CMV-DNA load, and data between two groups were compared. Pearson linear regression analysis was used to analyze the correlation between aqueous CMV-DNA load and injection times or treatment duration.Results:At the end of treatment, the median number of IVG in the affected eye was 7 (4, 9). The results of correlation analysis showed that the aqueous humor CMV-DNA load of the affected eye was related to the number of treatments [ R2=0.385, P<0.000 1, B=-0.237 log 10 copies/(ml·time)], and the duration of treatment [ R2=0.394, P <0.000 1, B=-0.301 log 10 copies/(ml·week)] were negatively correlated. Among the 28 eyes, 13 eyes (46.4%, 13/28) in the continuous decline group and 15 eyes (53.6%, 15/28) in the non-sustained decline group. Baseline visual acuity ( t=-1.223), intraocular pressure ( t=1.538), aqueous humor CMV-DNA load ( t=-0.109), retinitis lesion area ( Z=-0.308) in the continuous decline group and the non-continuous decline group), the number of quadrants involved ( Z=-0.024) and whether the macula was involved ( Z=-1.826), combined with anterior segment inflammation ( Z =-0.499), combined with high intraocular pressure ( Z=-1.342), terminal visual acuity ( t =-0.845), intraocular pressure ( t=-0.068), total IVG times ( Z=0.907), age ( Z=-0.832), gender composition ( Z=-1.074), etc. The difference was not statistically significant ( P>0.05). Conclusion:The CMV-DNA load in aqueous humor decreases by about 50% every week during the treatment of CMVR eyes after Allo-HSCT; the transient increase in the CMV-DNA load in the aqueous humor during treatment does not affect the treatment process and clinical prognosis.
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Extended inflammation and cytokine production pathogenically contribute to a number of inflammatory disorders. Formosanin C (FC) is the major diosgenin saponin found in herb Paris formosana Hayata (Liliaceae), which has been shown to exert anti-cancer and immunomodulatory functions. In this study, we aimed to investigate anti-inflammatory activity of FC and the underlying molecular mechanism. RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS) or pretreated with FC prior to being stimulated with LPS. Thereafter, the macrophages were subjected to analysis of the expression levels of pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E2 (PGE), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, as well as two relevant enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The analysis revealed that FC administration blunted LPS-induced production of NO and PGE in a dose-dependent manner, while the expression of iNOS and COX-2 at both mRNA and protein levels was inhibited in LPS-stimulated macrophages pre-treated with FC. Moreover, LPS stimulation upregulated mRNA expression and medium release of TNF-α, IL-1β, and IL-6, whereas this effect was blocked upon FC pre-administration. Mechanistic studies showed that inhibitory effects of FC on LPS-induced inflammation were associated with a downregulation of IκB kinase, IκB, and p65/NF-κB pathway. Taken together, these data suggest that FC possesses an inflammation-suppressing activity, thus being a potential agent for the treatment of inflammation-associated disorders.
ABSTRACT
Extended inflammation and cytokine production pathogenically contribute to a number of inflammatory disorders. Formosanin C (FC) is the major diosgenin saponin found in herb Paris formosana Hayata (Liliaceae), which has been shown to exert anti-cancer and immunomodulatory functions. In this study, we aimed to investigate anti-inflammatory activity of FC and the underlying molecular mechanism. RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS) or pretreated with FC prior to being stimulated with LPS. Thereafter, the macrophages were subjected to analysis of the expression levels of pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E2 (PGE), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, as well as two relevant enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The analysis revealed that FC administration blunted LPS-induced production of NO and PGE in a dose-dependent manner, while the expression of iNOS and COX-2 at both mRNA and protein levels was inhibited in LPS-stimulated macrophages pre-treated with FC. Moreover, LPS stimulation upregulated mRNA expression and medium release of TNF-α, IL-1β, and IL-6, whereas this effect was blocked upon FC pre-administration. Mechanistic studies showed that inhibitory effects of FC on LPS-induced inflammation were associated with a downregulation of IκB kinase, IκB, and p65/NF-κB pathway. Taken together, these data suggest that FC possesses an inflammation-suppressing activity, thus being a potential agent for the treatment of inflammation-associated disorders.
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Objective@#To explore the acute toxicity of Diquat in mice and to calculate the median lethal dose (LD50) of Diquat to rats and observe the pathological changes of tissues and organs in rats with different concentrations of Diquat.@*Methods@#Diquat solution of 50 mg/kg was prepared freshly with 1 000 mg of Diquat and dilute the solution with water to a total of 20 ml. A total of 99 healthy adult male Wistar rats were randomly divided into part one, part two and control groups. In the first part, 36 rats were randomly divided into 4 groups: 100 mg/kg group, 200 mg/kg group, 300 mg/kg group and 400 mg/kg group, which were treated with 100 mg/kg, 200 mg/kg, 300 mg/kg and 400 mg/kg of Diquat solution by gavage, respectively. The death and symptoms of poisoning after intragastric administration were recorded, and the maximum tolerated dose and absolute lethal dose were measured. In the second part, 54 rats were randomly divided into 6 groups: 200 mg/kg group, 220 mg/kg group, 240 mg/kg group, 260 mg/kg、280 mg/kg group and 300 mg/kg group, whichwere treated with 200 mg/kg, 220 mg/kg, 240 mg/kg, 260 mg/kg, 280 mg/kg and 300 mg/kg of Diquat solution by gavage, respectively. The survival of rats in different concentration of Diquat was observed and the LD50 was calculated by Excel processing the formula of Koch's method. The control group were given equal volume water under the same experimental conditions. And moreover, the lungs, kidneys, hearts, livers, and brain tissues were collected and fixed by formaldehyde, embedded by paraffin, and sectioned for histopathological light microscopy.@*Results@#The maximum tolerated dose was 240 mg/kg and the absolute lethal dose was 300 mg/kg. The LD50 of Diquat for Rats was 280.58 mg/kg. The high-dose group had significantly more organ damage than the low-dose group after diquat poisoning.@*Conclusion@#The determination of the half-lethal dose of diquat, at the same time observed multiple organs damaged in rats after the diquat quickly poisoned. Kidneys, lungs and heart might be the main organ which was heavily damaged. With the extension of observation time, the organ damage of rats exposed to small doses gradually stabilized.
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Objective@#To investigate an incident of mushroom poisoning and related clinical data.@*Methods@#A descriptive analysis was performed to investigate an incident of poisonous mushroom poisoning in Jinan, Shandong Province, China in July 2016. The clinical data of four patients were analyzed and summarized, and the causes of this incident and prevention and control measures were summarized.@*Results@#This incident of acute poisonous mushroom poisoning was caused by Lepiota brunneoincarnata. The patients mainly had digestive system symptoms, including nausea, vomiting, and severe abdominal pain, and later developed liver damage. After comprehensive rescue treatment, one patient died and three survived. The main clinical manifestation of the patient who died was multiple organ failure, especially liver failure.@*Conclusion@#This incident of poisoning was caused by Lepiota brunneoincarnata the residents ate by mistake.
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Objective@#To investigate the causes of peripheral vascular thrombosis in patients with paraquat poisoning.@*Methods@#The patients with paraquat poisoning who were admitted to our department in recent two years were observed to screen out the patients with large vessel thrombosis. The data on toxic exposure history, clinical features, and treatment were collected to analyze the causes of thrombosis in the patients with paraquat poisoning.@*Results@#Three patients had typical lower limb thrombosis. There was one case of right common femoral vein thrombosis, one case of bilateral calf muscle vein thrombosis, and one case of right calf superficial vein thrombosis and right calf muscle vein thrombosis.@*Conclusions@#After paraquat poisoning, the blood is in a hypercoagulable state and prolonged bed rest may increase the risk of thrombosis.
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Objective@#To investigation to an accident of occupational trichloroethylene explosion and analyze the clinical datas.@*Methods@#An investigation was carried out on the explosion of trichloroethylene in a place in shandong province in June 2016, and the clinical data of 4 patients with trichloroethylene poisoning were analyzed.@*Results@#The incident is caused by irregularities in workers, 4 patients were characterized by different levels of the respiratory system, nervous system, liver, and skin lesions. Among them, respiratory system damage was more prominent, mainly manifested as chemical bronchitis and pneumonia, after positive rescue and treatment all recovered and discharged.@*Conclusions@#Trichloroethylene leak can cause severe ex-plosion accidents, can cause workers of the respiratory system, nervous system, liver and skin lesions, mainly glucocorticoids comprehensive therapy has good curative effect.
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Objective@#To investigate and analyze the clinical data of tetramine poisoning in a family and prevent similar incidents from happening again.@*Methods@#The study was conducted in July 2016 in a fami-ly with thiamine poisoning in shandong province, and the clinical data were analyzed.@*Results@#In this case, there are six cases of poisoning caused by the tetramine poisoning, and the convulsions are the main clinical manifestations, and the blood perfusion can have a good effect on the severe patients. After positive treatment, all 6 patients were cured.@*Conclusions@#The tetramine poisoning can cause severe convulsion, although the country has banned the production and use of it, the tetramine poisoning case still exist and cannot be ignored.
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Objective@#To investigate an accident of occupational acute hydrogen sulfide poisoning, and to analyze related clinical data.@*Methods@#An investigation was performed for an accident of occupational acute hydrogen sulfide poisoning in a place in Shandong, China, in July 2016, and related clinical data were summarized.@*Results@#This was a typical accident of occupational acute hydrogen sulfide poisoning, and a lack of occupational protection and illegal operation were the major causes of this accident. Of all five patients, four experienced coma, toxic encephalopathy, and respiratory failure and were cured at last, and one had cortical syndrome after long-term treatment and died of pulmonary infection seven months later.@*Conclusions@#In case of occupational acute hydrogen sulfide poisoning, rescuers should help the persons who are poisoned reasonably and meanwhile ensure their own safety.
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Objective@#To establish to paraquat poisoning acute lung injury animal model to study the therapeutic effect of Salvia polyphenols acid salt of paraquat-induced acute lung injury.@*Methods@#Adult male Wister rats 120, were randomly divided into three groups: the paraquat exposure group, the start of the experiment to give a one-time 20% paraquat dope orally 50 mg/kg body weight of rats; salvianolate treatment group, the start of the experiment paraquat to give a one-time 20% the stock solution orally 50 mg/kg body weight of rats, and then given daily intraperitoneal injection of 200 mg/kg body weight of rats salvianolate; blank control group was given the same amount normal saline. The exposure group, the treatment group and control group rats were sacrificed after anesthesia in the 3rd, 7th, 14th, 21st day from the beginning of the experiment respectively, and taken out and preserved venous blood specimens and lung tissue to be tested. Venous detection heme oxygenase-1 (HO-1) , the lung tissue detection heme oxygenase-1 (HO-1) , hydroxyproline (HYP) . And do biopsy specimens from some of the lung tissue, HE and Masson staining observed by optical microscope.@*Results@#Compared with control group, model group 7, 14, 21 days had elevated levels of serum and lung tissue HO-1 (all P<0.05) ; Treatment group 3, 7, 14, 21 days increased (all P<0.05) , and 3, 7, 14 days is higher than the model group (compared with model group, P<0.05) . Compared with control group, treatment group 3 days and model group, 14, 21 days HYP content in lung tissue increased significantly (all P<0.05) ; 21 days, compared with model group, HYP content of treatment group reduce obviously, the difference was statistically significant (P<0.05) . Optical microscope observation, lung tissue damage and aggravated with the experimental increase in the number of days, inflammatory cell infiltration, alveolar septal fibrosis gradually formed. The treatment group experimental animal lung tissue to reduce inflammation, lung fibrosis relief.@*Conclusion@#Paraquat (50 mg/kg body weight) to fill the stomach can be induced model of acute lung injury in the rats. The serum HO-1 expression and HO-1, HYP content in lung tissue increased obviously in model rats. Salvia miltiorrhiza polyphenols acid salt to a certain degree and stage influenced the expression of HO-1 and HYP, relieve acute lung injury and pulmonary fibrosis, has certain curative effect in the treatment of paraquat poisoning.
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Objective@#To investigate a mass of occupational acute methyl bromide poisoning incident and analyzed their clinical data.@*Methods@#To investigate an incident a mass of occupational acute methyl bromide poisoning in occurred in Shandong province in November 2016, and the clinical datas of 3 cases of severe patients with methyl bromide poisoning were analysed.@*Results@#This event was a sudden occupational poisoning incident. Lack of vocational training and irregularities is the main reason for the accident 3 patients with nervous system, respiratory system, circulatory system, urinary system damage is given priority to, after comprehensive rescue treatment, 2 cases died and 1 case survived.@*Conclusions@#Methyl bromide can cause severe poisoning, has high mortality in patients with acute severe poisoning.
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Objective@#To study the therapy of cordyceps-astragalus-salvia miltiorrhiza in treating acute lung injury and pulmonary interstitial fibrosis induced by paraquat poisoning.@*Methods@#All 120 adult Wister male rats were randomly assigned to three groups, the paraquat poisoning group (rats were intragastric administration paraquat 50 mg/kg body weight once at the beginning) , the cordyceps-astragalus-salvia miltiorrhiza therapy group (rats were given cordyceps-astragalus-salvia miltiorrhiza 90 mg/kg body weight intragastric administration half an hour after paraquat was given, then the same dose was given once a day) ; control group (rats were intragastric administration with physiological saline) . At 7th, 14th, 21st, and 28th day rats were sacrificed postanesthetic respectively after paraquat exposure, sample of lung tissue, bronchoalveolar lavage (BAL) , and venous blood were collected. GSH, SOD, TNF-α, TGF-β1, and HYP in plasma, bronchoalveolar lavage (BAL) , and the lung homogenates were determined. Optical microscope was performed to examine pathological changes in lung.@*Results@#Each experimental time point paraquat group and the treatment group rats serum SOD content significantly lower than the control group (P<0.05) . Each experimental time point the treatment group rats serum SOD levels increased significantly than that of paraquat group (P<0.05) . Each experimental time point paraquat group rats serum GSH content significantly lower than that of the control group (P<0.05) . Treatment group rats 7 days time GSH content significantly lower than that of the control group (P<0.05) . Treatment group 21 days, 28 days GSH content was increased significantly than that of the paraquat group (P<0.05) . Each experimental time point paraquat group rats alveolar lavage SOD content was significantly lower than that of the control group (P<0.05) . Treatment group 7 days, 14 days time SOD content was significantly lower than that of the control group (P<0.05) , Treatment group 21 days, 28 days SOD content was increased significantly than that of the paraquat group (P<0.05) . Each experimental time point paraquat group and the treatment group rats alveolar lavage GSH content significantly were lower than that of the control group (P<0.05) . Treatment group days 14 and 21 days, 28 days GSH content was increased significantly than that of the paraquat group (P<0.05) . Each experimental time point paraquat group rats alveolar lavage TNF α levels was higher than that of the control group (P<0.05) . Treatment group 7 days, 14 days the rat alveolar lavage TNF α levels was higher than that of the control group (P<0.05) . Treatment group 21 days, 28 days TNF α content significantly was decreased than that of paraquat group (P<0.05) . Paraquat group days 14 and 21 days, 28 days HYP content was significantly higher than that of control group (P<0.05) . Treatment group 21 days HYP content was significantly higher than that of control group (P<0.05) . Treatment group 28 days time HYP content in lung tissue of rats was significantly decreased than that of the paraquat group (P<0.05) . Each experimental time point paraquat group rat lung tissue (tissue homogenate) TGF-β1 content was higher than that of the control group, the difference was statistically significant (P<0.05) . Under optical microscope, the tissue damage of lung was aggravated, and reduced after cordyceps-astragalus-salvia miltiorrhiza was administrated.@*Conclusion@#Cordyceps-astragalus-salvia miltiorrhiza can reduce inflammation factor releasing, and relieve lung injury. It has therapeutic effect on lung injury induced by paraquat poisoning.
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<p><b>OBJECTIVE</b>To investigate the effect of neutrophil gelatinase-associated lipocalin (NGAL) on prognosis of patients with type 2 hepatorenal syndrome (HRS).</p><p><b>METHODS</b>A total of 54 patients with type 2 HRS were included in the study, and stratified for analysis according to survival status at 6-month followup:survival group, n=25; death group, n=29. Single factor analysis was used to compare the betweengroup differences for levels of plasma NGAL, urine NGAL, renin, aldosterone, and blood biochemical indicators. The Cox proportional hazard regression model was used to assess the prognosis of patients with type 2 HRS. The F-test, t-test, chi-square test, Pearson's correlation analysis, and Cox regression model were used for the statistical analyses.</p><p><b>RESULTS</b>The HRS patients with liver cirrhosis showed significantly lower levels of hemoglobin, platelets and albumin (all P < 0.05), but significantly higher international normalized ratio and levels of aspartate aminotransferase, alanine arninotransferase, total bilirubin, direct bilirubin, serum creatinine, plasma NGAL, urine NGAL, renin and aldosterone (all P < 0.05). Plasma NGAL and urine NGAL were positively correlated with renin, aldosterone, blood creatinine, MELD score, Child-Pugh score and ascites (P < 0.05). The patients in the 6-month survival group showed significantly lower levels of albumin, serum sodium, serum creatinine, plasma NGAL, urine NGAL, renin, and aldosterone than those in the death group (P < 0.05), but significantly higher glomerular filtration rate (vs. death group, P < 0.05). The Cox proportional hazard regression model showed that MELD, plasma NGAL, total bilirubin and creatinine were influencing factors of 6-month prognosis for patients with type 2 HRS (relative risk: 1.214, 1.157, 1.098 and 1.016 respectively).</p><p><b>CONCLUSION</b>Plasma NGAL is high in patients with type 2 FHRS, and is associated with risk of death.</p>