Objective:To investigate the role and possible mechanism of edaravone dexborneol in the prevention and control of patho-logical injury of brain tissue around hematoma after intracerebral hemorrhage(ICH).Methods:A total of 176 Sprague-Dawley rats were randomly divided into sham-operation group,ICH group,edaravone group,and edaravone dexborneol group,with 44 rats in each group.All rats except those in the sham-operation group were used to establish a rat model of acute ICH,and each group was further di-vided into 1-day,3-day,7-day,and 14-day subgroups according to the time of evaluation,with 11 rats in each subgroup.At 2 hours after modeling,drugs were administered via intraperitoneal injection,i.e.,6 ml/kg normal saline for the sham-operation group and the ICH group,6 mg/kg edaravone for the edaravone group,and 7.5 mg/kg edaravone dexborneol for the edaravone dexborneol group,fol-lowed by subsequent administration every 12 hours until day 14.The modified Neurological Severity Score(mNSS)was used to assess neurological function;the wet-dry weight method was used to measure the water content of brain tissue;the biochemical methods were used to measure nitric oxide(NO)and total antioxidant capacity(T-AOC)in brain tissue around the hematoma;immunohistochemistry was used to measure the content of CD16 and CD206 in brain tissue around the hematoma.Results:The mNSS score on day 3(peak of the disease)was 0.6±0.5 for the sham-operation group,14.0±1.6 for the ICH group,9.8±0.8 for the edaravone group,and 10.4±1.1 for the edaravone dexborneol group,with a water content of 63.2±2.14,85.61±1.43,81.48±1.9,and 76.77±1.44,respectively,and the content of NO was 2.45±0.46,9.98±0.54,8.77±0.36,and 7.92±0.43,respectively;the content of T-AOC was 0.67±0.02,0.74±0.03,0.78±0.02,and 0.84±0.03,respectively;the content of CD16 was 143.8±15.82,3 673.81±166.33,2 970.74±132.75,and 2 521.69±140.74,respectively;the content of CD206 was 548.46±93.68,726±97.81,915.28±100.33,and 1 119.51±160.52,respectively.There were significant differences in these indica-tors between the edaravone dexborneol group and the other three groups(all P<0.05).Conclusion:Edaravone dexborneol can alleviate neurological deficit caused by ICH and exert a neuroprotective effect by reducing brain tissue edema around the hematoma,alleviating oxidative stress,and regulating the polarization of microglial cells.

Kidneys filter bloodand regulate fluid and electrolyte balances.However,the kidney is susceptible to toxicity of various compounds,Resulting in renal damage.Hence,prevention and treatment of renal injury is a hot research topic.Zebrafish is an ideal animal model,because it is closely related to humans in terms of morphology,physiology,and kidney functions and its response to compounds.In this article,we review the method and evaluation indexes of zebrafish kidney injury modeling.

Objective To study the expression of serum interleukin(IL)-17A,calcium binding protein S100A8 and S100A9 in children with severe Mycoplasma pneumoniae pneumonia(SMPP)and their prognostic significance.Methods A total of 116 children with SMPP who were diagnosed and treated in this hospital from March 2019 to March 2021 were enrolled as the SMPP group.According to the pediatric critical cases score,the SMPP children divided into non-critical group(43 cases),critial group(40 cases),extremely critical group(33 cases).According to the prognosis of 28 d after admission,the SMPP children were divided into a good prognosis group with 82 children and a poor prognosis group with 34 children.A total of 60 physical ex-amination of healthy children in the same hospital during the same period were enrolled as the control group.The levels of serum IL-17A,S100A8,S100A9,procalcitonin(PCT),C-reactive protein(CRP),IL-6 and tumor necrosis factor(TNF)-α were detected in each group.Pearson correlation analysis was used to analyze the cor-relation between serum levels of IL-17A,S100A8,S100A9 and PCT,CRP,IL-6,and TNF-α.Multivariate Lo-gistic regression analysis was used to analyze the factors affecting the poor prognosis of children with SMPP.The receiver operating characteristic(ROC)curve was used to analyze the value of each index in predicting the poor prognosis of children with SMPP.Results The SMPP group had significantly higher serum levels of IL-17A,S100A8,S100A9,PCT,CRP,IL-6,and TNF-α than the control group(P<0.05).In children with SMPP,the serum levels of IL-17A,S100A8,and S100A9 were positively correlated with PCT,CRP,IL-6,and TNF-α(P<0.05).The serum levels of IL-17A,S100A8 and S100A9 in extremely critical group were signifi-cantly higher than those in critical group and non-critical group(P<0.05).Elevated serum levels of IL-17A,S100A8 and S100A9 were independent risk factors for poor prognosis in children with SMPP.The area under the curve(AUC)of combined detection of serum IL-17A,S100A8 and S100A9 for predicting poor prognosis in children with SMPP was 0.895,which was higher than that of single detection of serum IL-17A,S100A8 and S100A9(0.833,0.764,0.810),the differences were all statistically significant(Z=3.780,6.723,5.012,P<0.059).The sensitivity and specificity of combined detection were 0.891 and 0.755,respectively.Conclu-sion The serum levels of IL-17A,S100A8 and S100A9 are increased in children with SMPP,which are related to the severity of SMPP.The combined detection of the three indicators has a high predictive value for the poor prognosis of SMPP.

Objective To discuss the sleep quality of hospitalized patients with rheumatic diseases and the factors affecting the quality of sleep. Methods With Pittsburgh sleep quality index ( PSQI) questionnaire and the self-designed questionnaire about the factors affecting sleep were used to survey 125 patients with rheumatic disease from November 2013 to October 2014 in a level three class A hospital in Beijing city. Results Rheumatoid disease inpatients PSQI scores between 7 to 12 points had 35 cases, accounted for 28. 0%, more than 12 points having 6 cases, accounted for 4. 8%, PSQI various dimensions of 93 patients with seven hours of sleep time and accounted for 74. 4%, sleep efficiency more than 85% having 115 patients and accounted for 92. 0%, but the poor quality of sleep group with 113 cases and accounted for 90. 4%, sleep time group 101 cases of patients and accounted for 80. 8%, patients with sleep disorders in 120 cases, accounted for 96%, 111 cases of patients with daytime dysfunction, accounted for 88. 8%, and used hypnotic drugs in patients with only 13 cases, accounted for 10. 4%, group of patients with rheumatic disease of the Pittsburgh sleep quality index was higher than normal group (P<0. 01); there was no significant difference in the total score of PSQI and in patients with glucocorticoid (P <0. 05). The percentage of poor sleep quality was in patients with more than sixty years old, not continue to work or study and poor sleep before hospitalization, and sleep quality of patients affected by physical discomfort (P<0. 01);the primary factors affected patients′sleep was psychological factors. Conclusions The hospitalized patients with rheumatoid disease sleep quality are poor, while psychological factors are the main factors affecting sleep and corticosteroids is not absolutely the influencing factors of sleep. The elderly, the length of sleep before good quality patients should attract the attention of nurses. Using your own sleep drugs can improve sleep quality. Evaluation and assessment of patients′sleep quality can find out potential problems.

Objective To observe the influence of coal-burning type of fluorosis on hypothalamic-pituitaryovary axis function and to explore possible mechanism in female rats.Methods Sixty SD rats were divided into two groups according to body weight with the method of random number table:control group and fluorosis group,30 rats in each group.Fluorosis group was feed with corn powder baked by high fluorine coal from Zhijin area.Changes of female rats' teeth during fluorine exposure were observed.After feeding for 180 days,24 h urine was collected in estrus and fluorine level was tested using fluoride ion-selective electrode; rats were executed and bone fluorine level was tested with high-temperature ashing-fluorine ion-selective electrode.Femoral artery blood was collected and serum was separated to test the contents of follicle stimulating hormone (FSH),luteinizing hormone (LH),testosterone (T),estradiol (E2) and progesterone (P) with electrochemiluminescence radioimmunoassay and gonadotropin-releasing hormone (GnRH),inhibin (INH) with enzyme-linked immunosorbent assay (ELISA),respectively.Organs,including hypothalamus,pituitary gland and ovary were weighted,and organ coefficients were calculated.Pathological morphology of hypothalamus,pituitary gland and ovary was observed after staining and ultrastructure of ovary was examined by electron microscopy.Results Coal-burning induced fluorine poisoning rat model was established successfully.There were no significant differences statistically in organ coefficients between fluorosis groups (0.032 ± 0.004,0.014 ± 0.008,0.037 ± 0.009) and controls (0.035 ± 0.005,0.012 ± 0.006,0.035 ± 0.004,t =0.46,0.87,0.64,all P ＞ 0.05).Rats serum GnRH,FSH,LH and T levels [(21.654 ± 4.765),(29.580 ± 5.221),(53.988 ± 6.506),(23.962 ± 2.255)μg/L] of fluorosis groups were all higher than those of controls [(10.384 ±2.250),(19.217 ± 4.743),(30.314 ± 4.443),(7.883 ± 1.973)μg/L,t =6.762,4.646,9.503,16.971,all P ＜ 0.05].But the level of P,INH [(12.635 ± 3.841),(18.926 ± 3.465)μg/L] were all lower than those of controls [(21.045 ±4.768),(48.076 ± 3.525)μg/L,t =4.344,18.649,all P ＜ 0.05].Serum E2 levels of control group and fluorosis group were (35.375 ± 10.662) and (27.500 ± 12.783)μg/L,respectively.The difference between groups was not statistically significant (t =1.821,P ＞ 0.05).No pathological changes were observed in the two groups of female hypothalamus,pituitary tissue by light microscopy and electron microscopy.Under light microscope,in the control group of normal ovarian tissue,more corpus luteum and different developmental stages of follicles were seen,granulosa cells were neatly arranged in a monolayer or multilayer.In fluorosis group,severe edema of ovarian interstitial cells and follicle degeneration increased.Cell structure and cell contours were blurred and unclear with occasional mature follicles.Under transmission electron microscope,in control group,normal ovarian granulosa cell ultrastructure was observed,nuclei were round,nuclear chromatin was uniform distributed,cytoplasm was rich in mitochondria and endoplasmic reticulum,and normal morphology.In fluorosis group,granulosa cells and interstitial cells showed apoptotic characters,such as nucleoli disappearing,mitochondrial swelling and chromatin aggregating at the nuclear membrane.Conclusions Fluorosis can induce ovarian tissue apoptosis,severely damage the micro environment.Reduction of P and INH affects ovarian,maturation and ovulation and leads to secretion of GnRH,FSH and LH.Fluorosis caused by coal-burning may induce the injury of ovary and cause abnormal secretion of hypothalamic-pituitary-ovary axis.Fluorosis has affected parts of female axis which may not be in the hypothalamus,pituitary,but causes ovarian tissue damage.

Objective To study the influence of fluorine on signaling pathway of osteoprotegerin(OPG)/ receptor activator of NF-κB ligand(RANKL) in cultured rat osteoblasts.Methods Osteoblasts were isolated from skull of neonatal rats(＜ 24 hours) by enzyme digestion,and fluorine of different concentrations [0 (control),1 × 10-3,1 × 10-4,1 × 10-5,1 × l0-6 and 1 × 10-7 mol/L] were added into the culture medium of second generation of osteoblasts.The expressions of OPG and RANKL mRNA were determined using real-time PCR 24 and 48 hours after culturing.The expressions of OPG and RANKL protein were measured by Western blotting.Results ① After exposed to fluorine for 24 hours,the differences of RANKL and OPG mRNA expression had statistical significance between groups(F =30.95,22.62,all P ＜ 0.01),the expression of RANKL mRNA(5.99 ± 0.39) in the 1 × 10-5 mol/L group and the expressions of OPG mRNA(3.52 ± 0.09,4.81 ± 0.15,3.68 ± 0.04) in the 1 × 10-4,1 × 10-5 and 1 × 10-6 mol/L groups were higher than those of the control group(3.20 ± 0.19,3.09 ± 0.58,all P ＜ 0.05),but in the 1 × 10-3 mol/L group,RANKL mRNA(2.29 ± 0.18) was lower than that of the control group(P ＜ 0.05).After exposed to fluorine for 48 hours,the differences of RANKL and OPG mRNA expression had statistical significance between groups(F =26.62,5.72,all P ＜ 0.01),the expressions of RANKL and OPG mRNA(6.67 ± 0.49 and 5.05 ± 0.51) in the 1 × 10-5 mol/L group were higher than those of the control group(4.29 ± 0.07 and 4.34 ± 0.12,all P ＜ 0.05),and in the 1 × 10-3 mol/L group the expression of OPG mRNA(3.63 ± 0.49) was lower than that of the control group(P ＜ 0.05).② The expression of RANKL protein was not statistically significant between 24 hours and 48 hours groups (F =0.07,0.49,all P ＞ 0.05) ; the differences of OPG protein expression had statistical significance between groups(F =3.26,P ＜ 0.05),the expression of OPG protein in the 1 × 10-5 mol/L group(1.45 ± 0.10) was higher than that of the control group(1.05 ± 0.06,P ＜ 0.05) at the 24 hours.After 48 hours,the expression of OPG protein was not statistically significant(F =0.44,P ＞ 0.05).Conclusions At lower fluorine concentrations,bone formation is the main activity.But when fluorine concentration increased and time prolonged,the osteoclast differentiation and maturation are promoted,and the bone resorption is the main thing.

Objective To observe the impact of coal-burning-borne fluorosis on the opening day of vagina,and estrogen cycle and endocrinology of female rat.Methods Ninety weaned two weeks and healthy female SD rats,weighing 60-80 g were selected,and divided into three groups by body weight using random number table:control group,moderate fluoride exposed group,and higher fluoride exposed group,thirty rates in each group.Rats in fluoride exposed groups were fed with baked corn collected from coal-burning-borne fluorosis areas containing different levels of fluorine(fluorine contents were 47.8 and 96.0 mg/kg,respectively) to establish coal-burning-borne fluorosis models.The corn fed to control group rats were collected from non-endemic areas (fluoride content was 5.2 mg/kg).After exposed to fluoride for 60,120 and 180 days,the rats were put to death during estrus in three batches (10 rats in every batche).The situation of female vaginal opening was observed and recorded every morning at 8:00 at the beginning of the experiment.Ten female rats in each group were randomly selected to observe vaginal exfoliated cells for 10 days continuously every morning,and HE staining was selected to discriminate estrogen cycle.Femoral artery blood was collected to observe the impact of estradiol(E2) in estrus.Results The vaginal opening day age of the longer fluoride exposed group [(49.0 ± 4.5)d] was longer than that of the control group[(45.4 ± 2.3)d] and the moderate fluoride exposed group[(46.7 ± 1.9)d,all P ＜ 0.05].Estrogen cycle of the longer fluoride exposed group[(5.8 ± 0.8)d] after fluoride exposure for 120 d was higher than that of the control group [(4.4 + 0.9)d] and the moderate fluoride exposed group [(4.9 ± 0.7)d,all P ＜ 0.05].Estrogen cycle increased with increasing dosage of fluoride after fluoride exposure for 180 d in three groups [control group:(4.3 ± 0.7)d,moderate fluoride exposed group:(5.4 ± 1.1)d,higher fluoride exposed group:(6.7 + 0.9)d,all P ＜ 0.05].Estrogen cycle in higher fluoride exposed group at 180 d[(6.7 ± 0.9)d] was higher than that of 60 d and 120 d[(5.2 ± 1.1),(5.8 ± 0.8)d,all P ＜ 0.05].At 60 d after exposed to fluoride,E2 levels of fluoride exposed groups were increased[control group:(30.125 ± 94.17)ng/L,moderate fluoride exposed group:(438.75 ± 71.80) ng/L],higher fluoride exposed group (456.25 ± 57.80)ng/L with increasing dosage of fluoride (all P ＜ 0.05).E2 level in rats exposed to fluoride for 180 d [(275.00 ± 127.83)ng/L] was lower than that of 60 d and 120 d [(456.25 ± 57.80),(392.50 ± 102.50)ng/L,all P ＜ 0.05] in higher fluoride exposed groups.Conclusions Coal-burning-borne fluorosis has a significant effect on vaginal opening day age,estrogen cycle and endocrinology of female rats.The higher the fluoride dose,and the longer the exposure time,the more severe the impact.

Objective To evaluate the treatment effect of compound Chinese medicine on skeletal fluorosis in rats by Micro-CT.Methods Eighty-eight Wistar rats which had been weaned for two weeks were divided into four groups according to body weight [(91.1 ± 10.0)g] by the method of random number table:control group(16 mts),middle fluorine(MF)group(24 rats),high fluorine(HF) group(24 rats),and high fluoride and low calcium low protein (HF-LC-LP) group (24 rats).The amounts of fluorine of MF,HF and HF-LC-LP groups were 50,100 and 100 mg/kg,respectively.The contents of calcium and protein in HF-LC-LP group were half of MF and HF groups.Six months after treatment with fluoride,eight rats of each group were put to death with femoral artery bleeding.The rest 16 rats of each fluorosis group were divided into two groups,one was the control group and the other was fed with both fluorine and the compound Chinese medicine which simulated the actual situation of fluorosis area.Each rat of the treatment group was given the medicine 194 mg/100 g for six days every week.Daily urine samples were collected when the medicine had been used for 0,30 and 60 days.All the rats were put to death with femoral artery bleeding after the medicine had beengiven for 90 days,and limbs bones were dissected.Urine fluoride was tested by the method of fluoride ion selective electrode ; bone fluoride was tested by the method of high temperature ashing-fluoride ion selective electrode; bone mineral density(BMD),tissue mineral density(TMD),structure model index (SMI),trabecular thickness (Tb.Th),trabecular separation (Tb.Sp),anisotropy (a1/a3),trabecular connection density(Conn.D),the volume ratio of trabecular and bone tissue,the ratio of bone surface area and volume(BS/BV),and trabecular number(Tb.N) were detected by Micro-CT technology.Results The level of urinary fluoride of high fluoride and low calcium low protein treatment group [(11.01 ± 3.67)mg/L] was lower than that of its control group [(34.32 ± 9.50)mg/L,t =3.13,P ＜ 0.05] when rats were remedied with the compound Chinese medicine for 60 days.The level of bone fluoride of high fluoride treatment group[(275.38 ± 171.65)mg/kg] was lower than that of its control group[(701.67 ± 178.16)mg/kg,t =5.42,P ＜ 0.05] when rats were remedied withy the compound Chinese medicine for 90 days; bone fluoride of high fluoride and low calcium low protein treatment group[(313.26 ± 124.51)mg/kg] was lower than that of its control group[(794.66 ± 261.35)mg/kg,t =3.25,P ＜ 0.05].The differences of Tb.Th,Tb.Sp,a1/a3,Conn.D,BV/TV,BS/BV and Tb.N among groups were statistically significant(F =2.785,2.681,3.039,27.231,2.595,2.854,5.050,all P ＜ 0.05).Tb.Th[(0.04 ±0.01)mm] and Tb.Sp[(0.03 ± 0.01)mm] of middle fluorine treatment group were higher than those of their control groups[(0.02 ± 0.00),(0.02 ± 0.00)mm,all P＜ 0.05]; al/a3,Corm.D,BV/TV and Tb.N[(0.77 ±0.61),(510.91 ± 304.99)mm-3,(0.42 ± 0.06) and (13.58 ± 2.48)mm-1] were lower than those of their control groups[(1.11 ± 0.01),(2 403.69 ± 124.02)mm-3,(0.46 ± 0.03) and (18.12 ± 0.69)mm-1,all P ＜ 0.05].BV/TV(0.44 ± 0.04) of high fluoride treatment group were lower than those of their control groups(0.49 ± 0.00,P ＜ 0.05) ; Tb.Th[(0.04 ± 0.01) mm] was higher than that of its control group [(0.03 ± 0.00)mm,P ＜ 0.05].Conclusion The compound Chinese medicine may has therapeutic effect on rat skeletal fluorosis.