Clinical characteristics and severe risk factors of tsutsugamushi disease / 中国热带医学

@#Abstract: Objective To investigate the clinical features and risk factors for severe tsutsugamushi disease, so as to provide reference for diagnosis and differentiation of severe tsutsugamushi disease as soon as possible. Methods The clinical data of 178 cases of inpatients with tsutsugamushi disease admitted to the Guangzhou Eighth People's Hospital, Guangzhou Medical University from January 2016 to September 2021 were collected and analyzed according to their gender, age, underlying diseases, clinical characteristics at admission, laboratory examination results within 24 hours of admission and epidemiological history. The patients were divided into the severe group and the non-severe group according to the diagnostic criteria. The data of clinical characteristics, laboratory examination and prognosis of the two groups were compared. Multivariate logistic regression analysis was performed on the variables with statistical significance and the receiver operating characteristic curve (ROC) was drawn. Results A total of 178 patients were included in this study, with 37 in the severe group and 141 in the non-severe group. Compared with the non-severe group, the age of the severe group was older, the underlying diseases were more, the incidence of dyspnea and the levels of white blood cell, total bilirubin, aspartate aminotransferase, lactate dehydrogenase, cystatin C, uric acid and serum creatinine were significantly increased, the levels of platelet and albumin were significantly decreased (all P<0.05). The dyspnea [odds ratio (OR value)=8.93, 95% confidence interval (CI): 1.200-66.424; P=0.032], total bilirubin (OR=1.091, 95%CI: 1.028-1.159; P=0.004) and serum creatinine (OR=1.052, 95%CI: 1.004-1.102; P=0.033) were independent risk factors for severe tsutsugamushi disease. The area under ROC curve of total bilirubin and serum creatinine were 0.777 and 0.764, respectively (both P<0.01), indicating high predictive value for severe tsutsugamushi disease. The optimal cut-off value for total bilirubin was 23.01 µmol/L, with a sensitivity of 54.10% and a specificity of 90.60%; the optimal cut-off value for creatinine was 126.45 µmol/L, with a sensitivity of 43.20% and a specificity of 100.00%. The case fatality rate of severe tsutsugamushi disease was 2.70%. Conclusions The patients with severe tsutsugamushi disease are older, and have more underlying diseases. Dyspnea, increased total bilirubin and elevated serum creatinine are independent risk factors for severe tsutsugamushi disease, which can help in the early identification of severe tsutsugamushi disease early.

Technical Note: Self-shielding evaluation and radiation leakage measurement of a jawless ring gantry linac with a beam stopper.

PURPOSE: To characterize the shielding design and leakage radiation from a newly released ring gantry linac (Halcyon, Varian Medical Systems). METHODS: To assess the radiation leakage surrounding headshield and the radiation level after the beam stopper, measurements were made with GafChromic films. To evaluate the in-room radiation levels, the radiation leakage in the isocenter plane was measured with a large volume spherical ionization chamber (Exradin A6, Standard Imaging). A lead enclosure was constructed to shield the chamber from the low energy scatter radiation from the room. The radiation level at multiple locations was measured with the MLC fully closed and gantry at 0, 45, 90, 135, 180, 225, 270, and 315 degrees. The leakage radiation passing through multiple concrete slabs with various thickness was recorded in a narrow beam geometry to determine the tenth value layer (TVL). RESULTS: A uniform leakage (<0.05%) at 1 m from electron beam line was measured surrounding the linac head with the maximum leakage measured at the top of the head enclosure. The highest radiation level (<0.08%) was measured near the edge of the beam stopper when projected to the measurement plane. The maximum radiation levels due to the head leakage at 15 locations inside the treatment room were recorded and a radiation map was plotted. The maximum leakage was measured at points that along the electron beam line while the gantry at 90 or 270 degree and at the end of head enclosure (0.314%, 0.4 m from electron beamline). The leakage TVL value is found to be 226 mm in a narrow beam geometry with the concrete density of 2.16 g/cm3 or 134.6 lb/cu.ft. CONCLUSION: An overall uniform leakage was measured surrounding linac head. The beam stopper shields the primary radiation with the highest valued measured near the edge of beam stopper. The leakage TVL values are derived and less than the values reported for conventional C-arm linac.

[Correlation of apolipoprotein AI, apolipoprotein B and their ratio with the severity of cerebral white matter lesions].

OBJECTIVE: To investigate the correlation of apolipoprotein AI (ApoAI), ApoB, ApoB/ApoAI and the severity of brain white matter lesions (WML). METHODS: A total of 648 patients with WML confirmed by brain magnetic resonance imaging (MRI) were divided into mild WML group (n=386) and moderate to severe WML group (n=262) according to evaluations with the Fazekas scale. The demographic data, blood biochemical parameters and the levels of ApoAI, ApoB and ApoB/AI ratio were compared between the two groups to identify the risk factors of moderate to severe WML. RESULTS: Univariate analysis showed that age, gender, hypertension, diabetes, coronary heart disease, previous stroke, homocysteine, HDL-C, ApoAI, and ApoB/AI ratio all differed significantly between the two groups (P < 0.05), but ApoB levels were similar between them (P > 0.05). Multivariate logistic regression analysis revealed that with ApoAI and ApoB/AI ratio as the continuous variables, after adjustment for the compounding factors, ApoB/AI ratio was an independent risk factor (OR=11.456, 95% CI: 3.622-36.229, P < 0.001) and ApoAI was an independent protective factor for moderate to severe WML (OR=0.068, 95% CI: 0.018-0.262, P < 0.001). With the upper quartiles of ApoAI level (1.38 g/L) and ApoB/AI ratio (0.58) as their respective cutoff values, patients with a high ApoAI level and a low ApoB/AI ratio were found to have the lowest incidence of moderate to severe WML (P < 0.001). CONCLUSIONS: An increased ApoB/AI ratio is an independent risk factor and an increased ApoAI level is an independent protective factor for moderate to severe WML.

Sulforaphane attenuates microglia-mediated neuronal necroptosis through down-regulation of MAPK/NF-κB signaling pathways in LPS-activated BV-2 microglia.

Sulforaphane (SFN), a natural dietary isothiocyanate in cruciferous vegetables such as broccoli and cabbage, has very strong anti-inflammatory activity. Activation of microglia leads to overexpression of a series of pro-inflammatory mediators, which play a vital role in neuronal damage. SFN may have neuroprotective effects in different neurodegenerative diseases related to inflammation. However, the mechanisms underlying SFN's protection of neurons against microglia-mediated neuronal damage are not fully understood. Here, we investigated how SFN attenuated microglia-mediated neuronal damage. Our results showed that SFN could not directly protect the viability of neurons following pro-inflammatory mediators, but increased the viability of BV-2 microglia and down-regulated the mRNA and protein levels of pro-inflammatory mediators including TNF-α, IL-1ß, IL-6 and iNOS in a concentration-dependent manner in BV-2 cells. SFN also significantly blocked the phosphorylation of MAPKs (p38, JNK, and ERK1/2) and NF-κB p65, both by itself and with MAPK inhibitors (SB203580, SP 600125, and U0126) or an NF-κB inhibitor (PDTC). The expression of pro-inflammatory proteins was also blocked by SFN with or without inhibitors. Further, SFN indirectly increased the viability and maintained the morphology of neurons, and the protein expression of RIPK3 and MLKL was significantly suppressed by SFN in neuronal necroptosis through p38, JNK, and NF-κB p65 but not ERK1/2 signaling pathways. Together, our results demonstrate that SFN attenuates LPS-induced pro-inflammatory responses through down-regulation of MAPK/NF-κB signaling pathway in BV-2 microglia and thus indirectly suppresses microglia-mediated neuronal damage.

The synthesis of molecular imprinted chitosan-gels copolymerized with multiform functional monomers at three different temperatures and the recognition for the template ovalbumin.

In this paper, the molecularly imprinted polymers (MIPs) were prepared to recognize the template ovalbumin. The graft copolymerization was conducted based on chitosan (CS) and several types of functional monomers, while choosing N,N-methylenebisacrylamide as the cross-linking agent. The influence of the synthesis temperature was investigated. The effect of different kinds of functional monomers was compared and optimized. The properties of the obtained gels were characterized by using the FT-IR spectrometer, field emission scanning electron microscope (FESEM) and Zeta-meter. The adsorption isotherms of the imprinted chitosan gels were determined and well fitted by a Langmuir model. The maximum theoretical adsorption capacities (Q(max)) was determined to be 9.74 mg g(-1) for the MIP (CS-g-AAm) and 22.94 mg g(-1) for the MIP (CS-g-MAA). Several types of reference protein with different molecular weights and isoelectric points were selected to examine the selectivity of the chitosan based gels. The results implied that the charge effect and the shape memory were the critical factors affecting the rebinding process. Finally, the selectivity for the protein mixture adsorption was evaluated by the high efficiency liquid chromatography (HPLC) analysis choosing lysozyme as the competitive protein. These results demonstrate the potential selectivity of the prepared chitosan gels.

Ovca1, a candidate gene of the genetic modifier of Tp53, Mop2, affects mouse embryonic lethality.

In this study, we show genetic modifier genes of Tp53 that can exacerbate embryonic abnormalities. Using a mouse model in which CE/J mice were crossed with the Tp53-null 129/Sv (129-Trp53(tm1 Tyj)) mice, a subset of Tp53+/- and -/- male and female embryos died during gestation. Our hypothesis, based on the genotypes of survivors, is that two genetic modifiers and a Tp53 null allele lead to an increase in embryonic lethality. We previously identified a recessive modifier (Mop1) from CE/J mice on chromosome 11 centromeric to Tp53. We have uncovered a dominant modifier (Mop2) from 129/Sv mice telomeric to Tp53. We discovered a polymorphic change (321P-->321S) of Ovca1 within the Mop2 locus of CE/J mice. This polymorphism increased both mRNA and protein levels of OVCA1 in various tissues. CE/J primary cells cultured from different tissues proliferated more rapidly than 129/Sv cells. In addition, CE/J cells cycled while 129/Sv cells had a higher arrest in the G1 phase. Transfection of Ovca1 containing the 321P polymorphism into CE/J cells caused a higher G1 arrest. The pattern of OVCA1 expression also changed from being diffuse throughout the cytoplasm in 129/Sv cells to being punctuate in the cytoplasm of CE/J cells. Tp53+/- abnormal embryos had more proliferating cells than normal embryos, but no obvious difference in differentiated neuronal cells. Tp53-/- small embryos had less differentiated neuronal cells and proliferating cells than normal embryos. Thus, a polymorphism of Ovca1, combined with Mop1, genetically modifies embryonic lethality in Tp53 deficient mice.

[Investigation of the status of ophthalmology in China].

OBJECTIVE: To identify the quantity, constitution, distribution, human resources, medical service, equipment utilization conditions of our ophthalmic organizations. METHODS: Adopt the ophthalmology status survey forms developed by the Department of Health Administration of Ministry of Health and Office of National Committee for Prevention of Blindness to investigate the registered medical treatment organizations in the whole mainland of China in 1996. The collected data were analyzed using SAS software. RESULTS: There were 4,151 ophthalmological organizations, 43,204 beds for ophthalmic patients, 22,577 eye doctors, and 16,448 ophthalmic nurses in China in 1996. 41.55% of eye doctors worked in the general hospitals above the county level. CONCLUSION: The distribution of ophthalmic organizations and human resource is uneven. It may be the main cause to restrict the activities for prevention of blindness in China.

[Pressure influence on mRNA and protein expression of inducible nitric oxide synthase in purified retinal ganglion cells of rats].

OBJECTIVE: To study the inducible nitric oxide synthase (iNOS) mRNA and protein expression in rat purified retinal ganglion cells (RGCs) that cultured under different pressures. METHODS: (1) To culture RGCs that from Sprague Dawley (SD) neonatal rats (postnatal 1 - 5 days) on two planes in assimilative culture solution, RGCs were purified by Thy1.1 with sheep anti rat FITC monoclonal antibody. (2) RGCs were cultured under pressures of 0, 20, 40, 60 and 80 mm Hg, respectively. The changes of iNOS mRNA and protein in RGCs under different pressures were demonstrated qualitatively and quantitatively by in situ hybridization, RT-PCR and Western blot. RESULTS: After cultured for 12 and 24 hours in vitro, the purification rate of RGCs in the experiment reached 98%. The expression of iNOS mRNA and protein in RGCs became higher and higher as the pressure was increased. There were no iNOS mRNA and protein expression in the control group (0 mm Hg) and weak expression in 20 mm Hg group (P < 0.05). 40, 60 and 80 mm Hg groups had a very significant difference from the control group, respectively (P < 0.01). CONCLUSION: Pressure can evoke the expression of nitric oxide synthase mRNA and protein in purified retinal ganglion cells in vitro, thus the nitric oxide can be one of the causes of RGC damage, that may induce or aggravate glaucoma.

[Effect of pressure on proliferation and apoptosis of bovine trabecular meshwork].

OBJECTIVE: To investigate the effect of pressure on the expression of cell cycle and apoptosis related gene bcl-2 and bax mRNA by bovine trabecular meshwork cells. METHOD: Twenty mm Hg, 40 mm Hg, 60 mm Hg and 80 mm Hg(1 mm Hg = 0.133 kPa) pressure were given to the cultured trabecular meshwork cells respectively in the treatment groups. No pressure was given in the control groups. Each pressure sustained for 24 and 48 hours. Proliferation index, apoptosis index, bcl-2 and bax mRNA expression of trabecular meshwork cells were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling, flow cytometry and in situ hybridization. RESULTS: In 24 hour groups, there were no significant differences between the apoptosis index of control group and pressure /= 60 mm Hg. In 48 hour groups, apoptosis index, proliferative index and bax mRNA expression had significant differences from that of the control groups when pressure was >/= 40 mm Hg. CONCLUSION: Pressure >/= 40 mm Hg sustaining for a period of time can suppress trabecular meshwork cell proliferation and induce apoptosis through influencing bcl-2 family members.

Effects of nitric oxide on proliferation and apoptosis of cultured bovine trabecular meshwork cells.

The effects of different doses of nitric oxide (NO) on the proliferation and apoptosis of the cultured bovine trabecular meshwork (TM) cells were studied. L-arginine and NG-nitro-L-arginine methyl (L-NAME) were incubated with TM cells for 48 h. In the control group, no medicine was given. In the experimental groups, concentrations of L-arginine and L-NAME were 1 x 10(-7) mol/L, 1 x 10(-6) mol/L, 1 x 10(-5) mol/L, 1 x 10(-4) mol/L, 1 x 10(-3) mol/L and 1 x 10(-2) mol/L, respectively. NO2- in supernate, the proliferation and apoptosis of TM cells and mRNA expression of bcl-2 and bax were measured by Griess reagent, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL), MTT assay and in situ hybridization, respectively. The results showed that L-arginine with concentration > or = 1 x 10(-4) mol/L could induce apoptosis of the TM cells and inhibit the proliferation of TM cells through increasing the NO levels, down-regulating bcl-2 mRNA expression and up-regulating bax mRNA expression; L-NAME with concentration > or = 1 x 10(-5) mol/L could induce the proliferation of the TM cells through suppressing the production of NO. It was concluded that NO in high level could induce apoptosis of the TM cells and suppress the proliferation of the TM cells.