Objective:To evaluate the effect of extracorporeal shock wave on the phosphoproteomics of the spinal cord in rats with diabetic neuralgia.Methods:Thirty-six healthy male SPF-grade Sprague-Dawley rats, aged 2 months, weighing 200-250 g, were divided into 3 groups ( n=12 each) using the random number table method: control group (group C), diabetic neuralgia group (group D), and extracorporeal shock wave + diabetic neuralgia group (group E). The rats were continuously fed a common diet in group C, while the rats were fed a high-sugar and high-fat diet for 8 weeks in D and E groups. Streptozotocin 35 mg/kg was intraperitoneally injected, and the successful induction of diabetic neuralgia was defined as the blood glucose >14.6 mmol/L and the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) ≤85% of baseline values. Group E received extracorporeal shock wave treatment after developing the model, with 1, 000 shocks per session at a frequency of 10 Hz and an energy of 1.0 bar, once per week for a total of 4 sessions. The MWT and TWL were measured before developing the model (T 0) and at 1, 2, 3 and 4 weeks after developing the model (T 1-T 4). After the last extracorporeal shock wave treatment, the rats were anesthetized and sacrificed, and lumbar spinal cord tissues were obtained for proteomic analysis and for detection of the expression of glial fibrillary acidic protein (GFAP), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) (by immunohistochemistry). Results:Compared with group C, the MWT and TWL were significantly decreased at T 1-T 4 in D and E groups ( P<0.05). Compared with group D, the MWT and TWL were significantly increased at T 1-T 4 in group E ( P<0.05). The results of phosphoproteomics screening revealed 284 differentially phosphorylated proteins in D and C groups, 282 in E and C groups, and 303 in E and D groups ( P<0.05). The results of immunohistochemistry showed that the expression of GFAP, IL-1β and TNF-α was significantly up-regulated in group D compared with group C ( P<0.05); the expression of GFAP, IL-1β and TNF-α was significantly down-regulated in group E compared with group D ( P<0.05). Conclusions:The mechanism by which extracorporeal shock wave alleviates diabetic neuralgia is related to inhibition of astrocyte activation and excessive phosphorylation of mGluR5 in rats.

Objective To observe the effects of folic acid(FA)supplementation on the expression of Flotillin-1 and β-amyloid protein(Aβ)-metabolism-related proteins in the brains of inflammation-stimulated Alzheimer's disease(AD)mice.Methods Twenty-seven 6-month-old male APP/PS1 mice were randomly divided into AD,AD+LPS,and AD+LPS+FA groups,with nine mice in each group.Nine C57BL/6J male mice born within the same month were used as the Control group.The AD+LPS+FA group was given folic-acid-supplemented feed(8 mg/kg)for 3 months of intervention,while the other three groups were fed normal feed.Lipopolysaccharide solution(LPS,250 μg/(kg·d))was injected intraperitoneally into mice in the AD+LPS and AD+LPS+FA groups 1 week before the end of the experiment,and saline was injected into the remaining two groups.The serum inflammatory factors TNF-α and IL-6 levels and brain tissue Aβ1-40 and Aβ1-42 levels of mice in each group were detected by ELISA.Flotillin-1 protein expression in brain tissue was detected using Western blot,and the co-expression of Flotillin-1 and Aβ1-42/APP/PS1/BACE1 in the cortical region of the brain was detected via immunofluorescence double-labeling.Results After ANOVA analysis,we found mice in the AD group had elevated serum TNF-α and IL-6 levels(P＜0.05),elevated levels of Aβ1-40 and Aβ1-42(P＜0.05),increased expression of Flotillin-1 protein(P＜0.05),and increased co-expression of Flotillin-1 and Aβ1-42/APP/PS1/BACE1 in the cortical brain tissue(P＜0.05)compared with the Control group.Compared with mice in the AD group,those in the AD+LPS group had further increases in serum inflammatory factors and Aβ levels in the brain(P＜0.05)and increased co-expression of Flotillin-1 and Aβ1-42/APP/BACE1 double-labeled proteins in their cortical brain tissue(P＜0.05).Compared with mice in the AD+LPS group,those in the AD+LPS+FA group had lower in vivo inflammation levels and Aβ content in the brain(P＜0.05),lower brain tissue Flotillin-1 protein expression(P＜0.05),and lower Flotillin-1 and Aβ1-42/APP/PS1/BACE1 protein co-expression in cortical brain tissue(P＜0.05).Conclusions Folic acid supplementation may reduce Flotillin-1 protein expression and Aβ deposition in the brain of AD inflammatory mice.

Objective:To evaluate the effect of intravenous infusion of lidocaine on the efficacy of conventional treatment for rheumatoid arthritis.Methods:Forty-four patients with rheumatoid arthritis of either sex, aged 32-85 yr, weighing 40-76 kg, who were admitted to the Department of Pain and Nephrology in our hospital from September 2019 to September 2020, were divided into 2 groups ( n=22 each) according to the random number table method: control group (C group) and lidocaine group (L group). Both groups received conventional treatment.When visual analogue scale (VAS) score ≥5, glucocorticoid (GC) and non-steroidal anti-inflammatory drugs (NSAIDs) were taken orally to maintain the VAS score ≤4.In group L, 0.2% lidocaine hydrochloride injection 3 mg/kg (diluted with 0.9% sodium chloride injection 500 ml) was intravenously infused at a rate of 25 ml/h for 2 h, once a day, for 5 consecutive days, based on the conventional treatment.The VAS score, 28-joint Disease Activity Score (DAS28 score), simplified disease activity index score (SDAI score), consumption of GC and NSAIDs and adverse reactions were recorded before treatment (T 1) and at 1, 4 and 8 weeks after treatment (T 2-4). The temperature of the pain area of the affected joint was evaluated through infrared thermal imaging at T 1 and T 2. Results:Compared with the baseline at T 1, VAS score, DAS28 score and SDAI score were significantly decreased at each time point, and the temperature of the pain area of the affected joint at T 2 was decreased in the two groups ( P<0.05). There were no significant differences in VAS score, DAS28 score and SDAI score at each time point between two groups ( P>0.05). Compared with group C, the consumption of GC and NSAIDs was significantly decreased, and the temperature of the pain area of the dorsum of both hands and the dorsum of right foot at T 2 and incidence of adverse reactions were decreased in group L ( P<0.05). Conclusions:Intravenous infusion of lidocaine can optimize the efficacy of conventional treatment for rheumatoid arthritis.

OBJECTIVE：To study the improvement effects of ica riin（ICA）on cognitive function in schizophrenia model rats and its mechanism. METHODS ：SD rats were divided into blank control group ，model group ，ICA low-dose ，medium-dose and high-dose groups （15，30，60 mg/kg）. Except for blank control group ，other groups were given N-methyl-D-aspartate receptor antagonist MK- 801（0.2 mg/kg）intraperitoneally to induce schizophrenia rats models ，once a day ，for consecutive 14 days. After modeling，ICA groups were intragastrically administered with the corresponding drugs ，while blank control group and model group were intragastrically administered with the same volume of water ，once a day ，for consecutive 7 days. The behavioral com changes of rats were detected by Morris water maze test ，open field test ， forced swimming test and Y maze test pathological changes of hippocampus were observed by Nissl staining；the levels of cholinergic indexes [acetylcholine （Ach），choline acetyltransferase （ChAT） and acetylcholinesterase （AchE）] in cerebral tissues were detected by ELISA. The expression of BDNF ，ERK and CREB mRNA in cerebral tissue were detected by RT-PCR ；expression or phosphorylation level of BDNF ，ERK，CREB protein ，apoptosis related proteins （Bcl-2，Bax and Caspase- 3）were detected by Western blot. RESULTS ：Compared with blank control group ，escape latency ，distance at T 1-T3， cumulative immobility time and the expression of Caspase- 3 protein in cerebral tissues were significantly increased in model group （P＜0.05）；the times of crossing platform ，alternation rate ，the number of Nissl staining positive neurons in hippocampus tissues ， the levels of Ach and ChAT in cerebral tissues ，Bcl-2/Bax ratio ，mRNA and protein expression of BDNF ，mRNA expression of ERK and CREB ，the phosphorylation of ERK 1/2 and CREB were significantly decreased （P＜0.05）.Compared with model group ， escape latency ，distance at T 1-T3，cumulative immobility time ，the number of Nissl staining positive neurons ，AchE level in cerebral tissues and relative expression of Caspase- 3 protein were significantly decreased in ICA high-dose group （P＜0.05）；the times of crossing platform ，alternation rate ，levels of Ach and ChAT in cerebral tissues ，Bcl-2/Bax ratio ，mRNA and protein expression of BDNF ，mRNA expression of ERK and CREB ，the phosphorylation of ERK 1/2 and CREB were increased significantly（P＜0.05）. Above indexes in ICA low-dose and medium-dose groups were partially improved significantly than model group（P＜0.05）. CONCLUSIONS ：ICA can improve cognitive function in schizophrenia model rats.Its mechanism may be related to regulating cholinergic system ，inhibiting neuronal apoptosis ，and promoting the expression of BDNF/ERK/CREB signaling pathway.

Objective:To evaluate the impacts of tissue heterogeneity on dose calculation of cervical brachytherapy by comparing the doses calculated by two clinically used dose calculation method and the CT image-based Monte Carlo (MC) method.Methods:This study retrospectively selected 11 patients with cervical cancer treated with 3D brachytherapy in Anhui Provincial Cancer Hospital from January 2018 to June 2020. The dose distribution of each plan was calculated via three methods, dose calculation method described in American Association of Physicist in Medicine(AAPM) Task Group No. 43 Report (TG43-BT), Acuros BV(BV-BT) used to perform accurate dose calculations in high-dose-rate (HDR) brachytherapy with phantom heterogeneity, and CT image-based EGSnrc tool kit used to perform Monte Carlosimulation (MC-BT). The dose volumes( V3 Gy, V6 Gy, V9 Gy, and V12 Gy), target volume doses( D98, D90, D50), D2 cm 3 of organs at risk (OARs) calculated by the three methods were compared. Results:The HRCTV D90obtained by TG43-BT was 6.274 Gy, which was even overestimated by around 5% compared to the result calculated by MC-BT. Meanwhile, TG43-BT overestimated the dose volumesand the target volume doses compared to MC-BT.Except for D50 and V12 Gy, the differences between the doses to tumor calculated by BV-BT and MC-BT were not statistically significant( P>0.05). There was also no significant statistical difference between the D2 cm 3 of rectum, small intestine, and sigmoid calculated by BV-BT and MC-BT ( P>0.05). In contrast, the dose to D2 cm 3 of bladder determined by MC-BT was 4.609 Gy, which was notably higher than those deter mined by TG43-BT and BV-BT. Conclusions:TG43-BT overestimated the doses to tumor targets and most OARs since the effects of tissue heterogeneity were not taken into consideration. BV-BT performed efficient calculation and most of the dose distributionin target volume and OARs obtained by BV-BT were consistent with that calculated by MC-BT. Nevertheless, low accuracy occurred for the regions near the sources and full bladder, which warrants further caution in clinical evaluation.

Objective:To investigate the impacts of the composition and physical density of tissue on the dose distribution of implanted 125I seeds, in order to provide references for the clinical dose calculation and assessment of implanted radioactive particles. Methods:The OncoSeed 6711 physical model of 125I seeds was established using thes of twareegs_brachy and was validated through the calculation of dose rate constant and the radial dose function [ g( r)] in water. Then, based on the element composition and physical density of different types of tissue, the g( r) and absorbed dose ratein water, prostate, breast, muscle, and bone were calculated. Results:The calculated dose rate constant (0.950 cGy·h -1·U -1) and g( r)in water approached the values in related literature. The absorbed dose in bone was 6.042 times than that in water at a distance of 0.05 cm from the implanted source. The difference between the absorbed doses in breast and water was more than 10% at a distance of less than 1.7 cm from the implanted source. The difference between the absorbed doses in prostate/muscle and water was less than 5% at the same radial location. Conclusions:The dose distribution of 125I seeds in some types of human tissue is significantly different from that in water, which should be carefully considered in clinical dose calculation.

Objective:To investigate the dosimetry differences in the treatment of locally advanced cervical cancer with intracavitary/interstitial brachytherapy (IC/IS BT), intracavity brachytherapy combined with intensity modulated radiotherapy (ICBT+ IMRT) and simple IMRT.Methods:Totally 16 patients with local advanced cervical cancer were retrospectively selected, which were treated by three-dimensional brachytherapy. On the basis of the original three-dimensional intracavitary/interstitial brachytherapy plan, ICBT+ IMRT and IMRT plans were designed respectively to study the dosimetry differences of target and different organs at risk for the three kinds of plans.Results:A total of 75 brachytherapy treatment plans were designed, including 25 IC/IS BT, 25 ICBT+ IMRT and 25 IMRT. There was not statistically significant difference of target dose parameters between ICBT+ IMRT and IC/IS BT plan ( P>0.05). ICBT+ IMRT plans had better OAR sparing than IC/IS BT. The doses of OARs in the IMRT plans were relatively large and the volume irradiated to more than 60 Gy ( V60) was significantly higher( t=6.77, 10.37, 4.61, 2.83, P<0.05). Conclusions:The ICBT+ IMRT technique not only provides better target coverage, but also maintains low doses to the OARS, which can be used as an alternative treatment to IC/IS BT. Although the target coverage of IMRT is better, the protection of OARs is not satisfied, so it is not suitable for local boost therapy of advanced cervical cancer.

Objective:To evaluate the application value of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) and dynamic contrast enhancement MRI (DCE-MRI) in the prediction of the early efficacy of concurrent chemoradiotherapy (CCRT) for cervical squamous cell carcinoma.Methods:Fifty patients with cervical squamous cell carcinoma confirmed by pathology were included. Before CCRT, IVIM-DWI and DCE-MRI were scanned, and the values of quantitative parameters including ADC, D, D * and f of IVIM-DWI and K trans, K ep, V e and V p of DCE-MRI before treatment were measured for all patients. MRI reexamination was performed 1 month after the end of CCRT, and all patients were divided into the cure group and the residual group according to the tumor remission. The parameters of IVIM-DWI and DCE-MRI before treatment were statistically compared between two groups. The optimal predictive parameters and predictive thresholds were determined by drawing the receiver operating characteristic (ROC) curve. Results:Twenty-four patients were assigned into the cure group and twenty-six patients in the residual group. The ADC, D and V e values before treatment in the cure group were significantly lower than those in the residual group (all P<0.05), whereas the f and K trans values were significantly higher than those in the residual group (both P<0.05). The other parameters did not significantly differ between two groups (all P>0.05). The area under ROC curve (AUC=0.823) of D value was the largest, followed by K transvalue (AUC=0.754). The combined prediction efficacy of D and K trans (AUC=0.867) was higher than that of either D or K trans alone. The sensitivity was 88.5%, 85.8% and 88.8%, and the specificity was 70.8%, 66.7% and 79.2%, respectively. Conclusions:Quantitative parameters of IVIM-DWI and DCE-MRI before treatment have certain predictive value for the early efficacy of CCRT in cervical squamous cell carcinoma, among which the predictive efficacy of D value is the highest, and the combined application of D and K trans can improve the predictive efficacy.

Objective To study the transport risk and factors that influence deaths of very low birth weight (VLBW) and extremely low birth weight (ELBW) infants.Method All infants transferred to our neonatal intensive care unit (NICU) by our hospital transport team or local hospital transport team from January 2014 to December 2015 were included in our study.Their clinical data were retrospectively studied.The risks of transport between hospitals were analyzed.The risk factors of deaths within and after 7 days of admission were further analyzed by multivariate Logistic regression analysis.The receiver operation characteristic (ROC) curve was used to assess the sensitivity and specificity of mortality index for neonatal transportation (MINT),transport related mortality score (TREMS),transport risk index of physiologic stability (TRIPS) for predicting mortality of preterm infants.Result (1) A total of 527 cases of ELBW/VLBW infants were included in our study.There were no deaths during transport.There were 10.2％ (54/527) died within and 8.9％ (42/473) died after 7 days of hospitalization.(2) Multivariate Logistic regression analysis showed that scleredema of newborn,secondary transport,gastrointestinal malformations,metabolic acidosis,high TREMS score,and high MINT score were risk factors of mortality within 7 days of admission for ELBW/VLBW infants;necrotizing enterocolitis,intraventricular hemorrhage ≥ three degree,high MINT score and low admission weight were risk factors of mortality after 7 days of admission.(3) The area under the ROC curve for MINT,TREMS,and TRIPS score were 0.672,0.655 and 0.665,respectively.The cut-off values for MINT score (cut-off 8,sensitivity 0.444,specificity 0.829),for TREMS score (cut-off 2,sensitivity 0.500,specificity 0.757,for TRIPS score (cut-off 20,sensitivity 0.444,specificity O.829) were selected to predict mortality within 7 days of admission.Conclusion (1) Secondary transport is the transport-related risk factor of mortality within 7 days of admission for ELBW/VLBW infants.(2) High MINT score is the risk factor of mortality within and after 7 days of admission.(3) If MINT ≥ 8,TREMS ≥2,or TRIPS ≥20,it might significantly increase the risk of mortality of ELBW/ VLBW infants within 7 days of admission after transport.

Objective To study the occurrence of bronchopulmonary dysplasia (BPD) in extremely low birth weight (ELBW) infants and to determine the risk factors of severe BPD.Method From January 2007 to January 2017,ELBW infants admitted to neonatal intensive care unit (NICU) in Hunan Children's Hospital were retrospectively analyzed.They were assigned into severe and mild/moderate groups based on the severity of BPD.The general condition,maternal status,prenatal and delivery room treatment,transportation,clinical courses,therapy and outcome in NICU of the two groups were compared,and the risk factors of severe BPD were analyzed.Result A total of 367 cases were hospitalized during the 10 years.281 ELBW infants with complete medical records survived longer than 28 days were enrolled in this study.Among them,233 had BPD.Among BPD infants,116 cases were in the severe BPD group,47 cases (40.5％) died.117 cases were in the mild/moderate BPD group and 1 case (0.9％) died.The difference between the two groups was statistically significant (P ＜ 0.05).Multivariate Logistic regression analysis showed that the risk factors of severe BPD were duration of mechanical ventilation ≥ 7 days (OR =7.518,95 ％ CI 3.197 ～ 17.676),ventilator-associated pneumonia (OR =3.047,95 ％ CI 1.436 ～ 6.464),1 min Apgar score ≤7 (OR =2.341,95 ％ CI 1.142 ～ 4.796) and patent ductus arteriosus (OR =2.223,95 ％ CI 1.079 ～4.582).Conclusion The incidence and mortality of BPD,especially severe BPD,are high in ELBW infants.Avoiding asphyxia,shortening the time of mechanical ventilation,preventing infection and closing ductus arteriosus are important measures to reduce the severity of BPD.