Celastrol is extracted from the traditional Chinese medicine Tripterygium wilfordii Hook.f..It is a kind of traditional Chinese medicine monomer with extensive pharmacological activity and has anti-tumor,anti-inflammation,anti-oxidation and neuroprotective effects.Studies have found that celastrol is not only closely related to obesity,tumor and cardiovascular diseases,but also plays a neuroprotective role in the cerebrovascular system by regulating various signaling pathways.At present,effective drugs for stroke are still limited,but with the deepening of the research on celastrol,its therapeutic potential in stroke has received more and more attention,especially in ischemic and hemorrhagic stroke,which has shown good therapeutic effects.Therefore,this is the first time to systematically summarize the therapeutic effects of celastrol on stroke and the underlying mechanisms involved,in order to provide further directions and references for the neuroprotective effects of celastrol.

Objective Platelet-to-lymphocyte ratio(PLR) has been proved to be a new biomarker of inflammation in various diseases. The purpose of this study was to explore the relationship between PLR and early neurological deterioration(END) in patients with acute ischemic stroke(AIS). Methods We retrospectively analyzed the clinical and laboratory data of 1 116 patients with AIS admitted to the Department of Neurology of Shanghai Yangpu District Central Hospital from May 2018 to October 2020.The patients were grouped for analysis according to whether END occurred within 72 hours. They were also grouped by the quartiles of PLR(platelet count divided by lymphocyte count). Univariable and multivariable logistic regression analyses were used to explore independent factors influencing END in patients with AIS. The predictive ability of PLR for the occurrence of END was evaluated by using a receiver operating characteristic(ROC) curve. Results A total of 1 116 patients with AIS were included in the study,with 125 patients(11.2%) in the END group and 991 patients(88.8%) in the non-END group. The univariable analysis showed that PLR in the END group was significantly higher than that in the non-END group(151.68 vs 132.89,P<0.05). The multivariable analysis showed that the risks of END in the PLR Q3 and Q4 groups were 2.172 times[odds ratio(OR)=2.172,95% confidence interval(CI) 1.201-3.929,P=0.01)]and 2.571 times(OR=2.571,95%CI 1.441-4.589,P=0.001) that of the PLR Q1 group. According to the ROC curve,the area under the curve for PLR predicting END was 0.587(95%CI 0.536-0.639,P< 0.001),and the optimal critical value was 119.40,with a sensitivity of 77.6% and a specificity of 39.4%. Conclusion PLR is an independent risk factor for END in patients with AIS. The increase of PLR is associated with a higher risk of END,which demonstrates certain predictive ability of PLR for the occurrence of END.

Objective:To evaluate the effect of intrathecal insulin-like growth factor-1 (IGF-1) on chemotherapy-induced neuropathic pain (NP) in mice.Methods:Forty clean-grade healthy male C57 mice, aged 7-9 weeks, weighing 22-24 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), chemotherapy-induced NP group (group CIPN), low-dose IGF-1 group (group I1) and high-dose IGF-1 group (group I2). In CIPN, I1 and I2 groups, oxaliplatin 5 mg/kg was intraperitoneally injected for 5 consecutive days to establish chemotherapy-induced NP model.Normal saline 0.2 ml was given in group C. After measurement of the pain threshold at 10 days after establishment of the model, IGF-1 0.5 and 1.0 μg were intrathecally injected in group I1 and group I2, respectively.Normal saline 5 μl was intrathecally injected in C and CINP groups.Mechanical withdrawal threshold (MWT) was measured at 3, 5, 8, 10, 11, 13 and 15 days after establishment of the model.After measurement of the pain threshold at 15 days after establishment of the model, the expression of spinal IGF-1, IGF-1receptor (IGF-1R), interleukin (IL)-17A, IL-1β and tumor necrosis factor (TNF)-α was detected, and IGF-1 positive cells were counted using immunofluorescence. Results:Compared with group C, MWT was significantly decreased, the expression of spinal IGF-1 was down-regulated, the count of IGF-1 positive cells was decreased, and expression of IL-17A, IL-1β and TNF-α was up-regulated at 3-25 days after establishment of the model in CINP, I1 and I2 groups ( P<0.05). Compared with group CIPN, MWT was significantly increased at 15 days after establishment of the model in group I1, and MWT was increased, the expression of spinal IGF-1 was up-regulated, the count of IGF-1 positive cells was increased, and expression of IL-17A, IL-1β and TNF-α was down-regulated at 13 and 15 days after establishment of the model in group I2 ( P<0.05). Compared with group I1, the count of IGF-1 positive cells in spinal dorsal horn was increased in group I2 ( P<0.05). There was no significant difference in the expression of spinal IGF-1R among the 4 groups ( P>0.05). Conclusion:Intrathecal IGF-1 can alleviate chemotherapy-induced NP, and the mechanism may be related to inhibiting the inflammatory responses in spinal cord of mice.

Objective　To analyze the risk factors of stroke-associated pneumonia (SAP) in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis.Methods　A total of 798 patients with AIS who received intravenous thrombolysis therapy with alteplase from the Department of Neurology,Yangpu Hospital,Tongji University from January 2016 to December 2020 were retrospectively selected and divided into pneumonia group and non-pneumonia group according to the presence or the absence of SAP.The clinical of the two groups were compared.Multivariate logistic regression analysis was used to analyze the independent risk factors of SAP.Results　Of 798 cases,115 cases occurred SAP.By multivariate logistic regression analysis,age≥70 years(OR=2.846,95%CI 2.311~5.083,P<0.001),diabetes(OR=2.291,95%CI 1.601~3.945,P=0.003),chronic obstructive disease(OR=2.064,95%CI 1.759~3.528,P=0.005),NIHSS score at admission>8(OR=1.814,95%CI 1.502~2.452,P<0.001),unconsciousness(OR=2.325,95%CI 2.005~3.404,P=0.008),dysphagia(OR=2.457,95%CI 2.221~4.017,P<0.001),hemorrhagic transformation(OR=1.828,95%CI 1.653~2.523,P=0.012) were independent risk factors of SAP in AIS patients treated with intravenous thrombolysis.Conclusion　Age≥70 years,diabetes,chronic pulmonary disease,NIHSS score at admission,unconsciousness,dysphagia,hemorrhagic transformation were independent risk factors of SAP in AIS patients treated with thrombolysis.

Objective:To evaluate the clinical efficacy and safety of modified chitosan eye drops on rabbit Candida albicans keratitis model.Methods:Ten healthy female New Zealand rabbits were used to establish the superficial Candida albicans keratitis model by the corneal surface lens method in the right eye.Slit lamp microscopy and corneal scraping and microscopic examination were performed to preliminarily determine whether the keratitis model has been successfully established, the rabbits were then randomly divided into a model group and a modified chitosan group by the random number table method.The successfully established rabbit models which were determined by fungal culture results were retained.Five normal rabbits receiving no intervention served as a normal control group.The experimental eyes in the normal control and modified chitosan groups were treated with modified chitosan eye drops, Six times a day for one week, and subsequently four times a day for one week.No treatment was administered to the model group.The changes of corneal lesions and ocular surfaces were examined by slit lamp microscopy every day.At 1, 7, 14, 21 and 28 days after modeling, the eye condition and corneal clinical scores was assessed by slit lamp microscopy.The corneal conditions in each group was observed for two weeks after drug withdrawal.Results:The corneal scraping and microscopic examination results of eight rabbits models showed that the fungal hyphae and spores were positive.The fungal culture results showed that the separated pathogen was Candida albicans.The success rate of modeling was 80%(8/10). The clinical scores in the model group at 7, 14 and 21 days after modeling were 14.50±0.58, 6.25±0.50 and 2.50±0.58, respectively, and were significantly higher than 7.25±1.26, 2.75±0.50 and 1.25±0.50 in the modified chitosan group (all at P<0.05). In the model group, corneal edema was significantly aggravated, and the central white ulcer area was enlarged within seven days after modeling.Between 7 and 28 days after modeling, the corneal ulcer was gradually healed, while the central corneal scar and neovascularization were remained.The average healing time was (24.5±2.6)days.In the modified chitosan group, the corneal infiltration was significantly alleviated within seven days after modeling, and the fungal hyphae and spores of corneal scraping were negative on the 14th day after modeling.The average healing time in the modified chitosan group was (13.5±1.3)days, which was significantly shorter than that in the the model group (P<0.01). No recurrence of keratitis was observed in the modified chitosan group after two weeks of drug withdrawal.The cure rate was 100%.In the normal control group, the conjunctival hyperemia, corneal edema, and lesions were not observed during topical administration.Conclusion:The treatment with modified chitosan eye drop is effective in a rabbit superficial Candida albicans keratitis model, and have no obvious toxic effects on ocular tissues.

To investigate the effects of ultrasound combined with microbubbles on intracellular Ca2+ homeostasis in carboplatin ( CBP )‐treated A549 cell and its possible mechanisms of inhibiting A549 cell line activity . Methods According to whether SonoVue was used or not ,and the different dose of CBP ,the groups A‐F were arranged as the ultrasound( US) group( group A ) ,the ultrasound combined with microbubbles ( USMB) group( group B) ,the low dose CBP ( 100 μg/ml) + US group( group C) ,the low dose CBP+USMB group( group D) ,the high dose CBP ( 200 μg/ml)+ US group ( group E) and the high dose CBP+USMB group( group F) .A549 cells were bathed and washed by a calcium‐free buffer , loaded with Ca2+ indicator fluo‐4 AM . Real‐time images were acquired using laser confocal microscopy . T he fluorescence intensity of intracellular calcium ion concentration ( [ Ca 2+ ] i ) in individual living cell was observed and the calcium overload was analyzed . Results After ultrasound irradiation ,the normalized fluorescence intensity of [ Ca2+ ] i increased rapidly ,then returned to a new homeostasis ( selected cells in groups A ,B ,E ,F ) or experienced a second calcium oscillation ( some cells in group C and D ) . All the selected cells in group B and some cells in group C and D exhibited superimposed oscillations . T he calcium overloading time in group D was longer than those of any other groups . Four cells in group A experienced delayed calcium oscillations . Compared with group A ,the selected cells in other groups exhibited a larger amplitude of calcium oscillation ( all P ＜ 0 .05 ) and the selected cells in group B and D exhibited calcium oscillation for a longer period of time( all P ＜0 .05) . Conclusions In the calcium‐free buffer ,US ,USMB , CBP+ US ,CBP + USMB are direct stimuli of calcium overload in A 549 cells . SonoVue ,CBP ,CBP +SonoVue are all synergistic stimuli of calcium overload in A 549 cells irradiated by ultrasound .US ,USMB and CBP may synergistically induce calcium release from intracellular store sites in A 549 cells . Calcium overload is a possible mechanism of ultrasound combined with microbubbles in assisting CBP chemotherapy .

Objective To investigate the effects of ultrasound combined with microbubbles on intracellular Ca2+ homeostasis in carboplatin ( CBP )-treated A549 cell and its possible mechanisms of inhibiting A549 cell line activity . Methods According to whether SonoVue was used or not ,and the different dose of CBP ,the groups A-F were arranged as the ultrasound(US) group(group A) ,the ultrasound combined with microbubbles ( USMB) group( group B) ,the low dose CBP ( 100 μg/ml) + US group( group C) ,the low dose CBP+USMB group( group D) ,the high dose CBP ( 200 μg/ml)+ US group ( group E) and the high dose CBP+USMB group( group F) .A549 cells were bathed and washed by a calcium-free buffer , loaded with Ca2+ indicator fluo-4 AM . Real-time images were acquired using laser confocal microscopy .The fluorescence intensity of intracellular calcium ion concentration ([Ca2+ ]i) in individual living cell was observed and the calcium overload was analyzed . Results After ultrasound irradiation ,the normalized fluorescence intensity of [Ca2+ ]i increased rapidly ,then returned to a new homeostasis (selected cells in groups A ,B ,E ,F) or experienced a second calcium oscillation ( some cells in group C and D) . All the selected cells in group B and some cells in group C and D exhibited superimposed oscillations . The calcium overloading time in group D was longer than those of any other groups . Four cells in group A experienced delayed calcium oscillations . Compared with group A ,the selected cells in other groups exhibited a larger amplitude of calcium oscillation( all P < 0 .05) and the selected cells in group B and D exhibited calcium oscillation for a longer period of time( all P <0 .05) . Conclusions In the calcium-free buffer ,US ,USMB , CBP+ US ,CBP + USMB are direct stimuli of calcium overload in A 549 cells . SonoVue ,CBP ,CBP +SonoVue are all synergistic stimuli of calcium overload in A 549 cells irradiated by ultrasound .US ,USMB and CBP may synergistically induce calcium release from intracellular store sites in A 549 cells . Calcium overload is a possible mechanism of ultrasound combined with microbubbles in assisting CBP chemotherapy .

Objective To observe the incidence of malnutrition, the therapeutic effect of nutritional support and the prognosis of patients with chronic obstructive pulmonary disease (COPD) under mechanical ventilation (MV) in patients with different traditional Chinese medicine (TCM) syndrome types and discuss the relationships between these indicators and the differentiation of cold-heat/deficiency-excess syndrome. Methods One hundred and three patients with COPD and MV admitted to Zhuji Hospital of TCM from September 2015 and July 2017 were enrolled, according to the different TCM syndromes, they were divided into an excess-heat syndrome group 42 cases and an asthenia-cold syndrome group 61 cases, and the differences in nutrition indexes and prognosis between the two groups were compared. Results The acute physiology and chronic health evaluationⅡ (APACHE Ⅱ) score, nutritional risk screening 2002 (NRS2002) score and the incidence of malnutrition in excess-heat syndrome group were significantly lower than those in the asthenia-cold syndrome group, while the body mass index (BMI) in excess-heat syndrome group was obviously higher than that in the asthenia cold syndrome group [APACHE Ⅱ score: 20.1±5.4 vs. 22.0±3.4,NRS2002 score: 5.2±0.6 vs. 6.2±0.8, incidence of malnutrition: 61.9% (26/42) vs. 80.3% (49/61), BMI (kg/m2): 22.6±3.8 vs. 19.9±4.8, all P < 0.05]. The levels of albumin (Alb), prealbumin (PA) and transferrin (TF) of the excess-heat syndrome group were higher than those in the asthenia-cold syndrome group, and the differences between the two groups were statistically significant on the 7th day under MV [Alb (g/L): 36.14±2.97 vs. 34.40±3.37, PA (mg/L): 237.67±28.01 vs. 185.34±30.86, TF (g/L): 2.13±0.38 vs. 1.95±0.12, all P < 0.05]. In the excess-heat syndrome group, the percentage of weaning from MV was higher than that of the asthenia-cold syndrome group [85.7% (36/42) vs. 65.6% (40/61)], the 28-day mortality [14.3% (6/42) vs. 31.1% (19/61)] and ICU stay time (days: 9.21±2.96 vs. 11.13±3.96) were lower than those of the asthenia cold syndrome group (all P < 0.05). Conclusion The analysis of TCM differentiation of cold-heat/deficiency-excess syndrome has a certain reference value to realize the changing rules in nutritional status and prognosis of patients with COPD under mechanical ventilation.

Objective To investigate the impact of ultrasound-targeted microbubble destruction ( UTMD) combined with carboplatin sustained release microspheres on the temperature of the tumor microenvironment and the concentration of the drug release in target tumor . Methods Twenty tumor bearing rabbits were randomly assigned into 4 groups : the control group without any treatment ; the carboplatin-loaded PLGA microspheres (CPMs) group ,only intratumoral injection of carboplatin sustained-release microspheres ;the S2000 group ,diagnostic ultrasound irradiation using S2000 equipment on local chemotherapy tumor tissue combined with lipid microbubbles ;the AP-170 group ,the same treatment as the S2000 group except the application of AP-170 instead of S2000 . Far-infrared thermography was performed to measure the tumor temperature . The experimental equipment of extracorporeal circulation was set up . The experimental conditions were assigned into 4 groups :37℃ CPMs group ,37℃ S2000 group ,37℃ AP-170 group ,40℃ AP-170 group . After irradiation experiment ,the carboplatin absorbance was measured at 229 nm wavelength . The absorbance difference of each group was compared with the 37℃ CPMs group ,and each group was tested 10 times . Results The intratumorous temperature in AP-170 group increased to (40 .24 ± 0 .72) ℃ ,which was significantly different from all the other groups ( P ＜ 0 .01).The in vitro drug release experiment showed that the absorbance in the 40 ℃ AP-170 group was 0 .1537 ± 0 .0094 ,which was significantly different from other groups ( P ＜ 0 .01).Higher temperature promoted the release of chemotherapeutic drugs from carboplatin sustained-release microspheres , thus enhanced the chemotherapeutic effect .This might be the mechanism that UTMD affects the microenvironment in this experiment .Conclusions UTMD increases the permeability of tumor cells .The increase of temperature promotes more drugs into the microenvironment of tumor cells .Thus ,the local chemotherapeutic effect is enhanced in the tumor .

Objective To investigate the relationship between family burden and support for maintenance hemodialysis ( MHD) patients. Methods Family APGAR index scale ( APGAR scale) and disease family burden scale ( FBS) were used to investigate among 126 MHD patients ( selected by convenient sampling method) from July 2012 to December 2013 in one Beijing level three class A hospital. Results The score of family burden was (36. 01 ± 7. 52) presented at 3 aspects of family economic burden, family daily life and family entertainment activities. The total score of family support was (7. 71 ± 3. 01), in which the good family function was 92 cases (73. 1%), family slightly obstacles 14 cases (11. 1%), and family serious obstacles 20 cases (15. 8%). The burden score of family having MHD patients had negative correlation with the score of family support (r= -0. 426, P<0. 05). Conclusions MHD patients′family support has significant influence on family burden. Therefore, the nursing staffs should strengthen the concept of holistic nursing care, pay more attention to the patients′family burden as well as nursing care, so as to perfect the family function, enhance the family support and comprehensively enhance the quality of care for patients.