Objective To analyze medication rules of traditional Chinese medicine in the treatment of thyroid nodules based on real-world data mining technology. Methods Chinese medicine prescriptions for patients with thyroid nodules as clinical first diagnosis in the Department of Thyroid and Breast Surgery in Qingdao Hospital of Traditional Chinese Medicine from August 2018 to August 2023 were collected, and the Traditional Chinese Medicine Inheritance Assistant Platform (V3.0) was used to analyze the medication rules. Results A total of 1 206 traditional Chinese medicine prescriptions for the treatment of thyroid nodules were screened, involving 291 traditional Chinese medicines; the top five most frequently used drugs were Fritillaria thunbergii, Prunella vulgaris, Bupleurum chinense, Poria cocos, and Pinellia ternata; the main function of drugs were clearing heat, tonifying deficiency, resolving phlegm, activating blood circulation, and regulating qi; the main property of the drugs was cold, the main tastes of drugs were bitter, sweet and spicy, and the meridians involved were mainly the lung, liver and spleen meridians; association rule analysis identified 17 high-frequency drug combinations, with Fritillaria thunbergii-Prunella vulgaris as the most frequently occurring drug pair; among the 16 association rules, Radix Scrophulariae-Fritillaria thunbergii and Rhizoma Cyperi-Bupleurum chinense had the highest confidence level; clustering analysis found 6 core drug combinations. Conclusion The main idea of clinical treatment of thyroid nodules in traditional Chinese medicine is to resolve phlegm and reduce nodules, promote qi circulation and blood circulation, and nourish qi and blood; the common herbal combination of Fritillaria thunbergii and Prunella vulgaris is used to clear heat, resolve phlegm, and reduce nodules, and the basic formula for resolving scrofula is based on Xiaoluo Pills, which resolves phlegm, softens hardened nodules, and reduces nodules.

In recent years, ultra-high dose rate (FLASH) radiotherapy has become one of the most advanced research topics in the field of radiotherapy. Experimental data indicate that FLASH radiotherapy can significantly reduce the irradiation damage in normal tissues while being as effective as clinical conventional dose rate radiotherapy in tumor control. The oxygen depletion hypothesis is considered as one of the key mechanisms underlying the FLASH effect. In this article, research progress on the discovery, experimental evidence and reaction principle of oxygen depletion was reviewed, the measurement methods and biological effect modeling methods of the oxygen depletion hypothesis were summarized, and the oxygen depletion difference between normal tissue and tumor was also discussed.

Objective To evaluate the effects of neural stem cells (NSCs) overexpressing brainderived neurotrophic factor (BDNF) on the levels of neurotrophic factors and microglia activation in hippocampus after brain irradiation.Methods Hippocampal NSCs were isolated from fetal rat brain and infected with GFP-lentivirus and GFP-BDNF-lentivirus.SD rats were randomized into four groups:control group,irradiated group (R group),GFP-modified NSCs transplantation group with irradiation (R+NSCs group),and GFP-BDNF modified NSCs transplantation group with irradiation (R+BDNF-NSCs group).NSCs were transplanted into the bilateral hippocampus of rats one month after whole brain irradiation at a single dose of 20 Gy.The expressions of BDNF,glial-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) in hippocampus were detected at 2 and 8 weeks after transplantation.The activation of microglia was observed by immunofluorescence.Results At 2 and 8 weeks after transplantation,the expressions of BDNF and NGF proteins in hippocampus of R+BDNF-NSCs group were significantly higher than those of R group (P＜0.05).The activated microglia in the R+NSCs group and the R+BDNF-NSCs group had no decrease compared with R group (P＞ 0.05).Conclusions The transplantation of NSCs overexpressing BDNF promotes the production of BDNF and NGF,which improves the level of neurotrophic factors in hippocampus after radiation.

Objective: To investigate the role of p75 neurotrophin receptor (p75NTR) in the irradiation-induced hippocampal neurogenesis impairment. Methods: Thirty Sprague-Dawley rats were subject to whole brain irradiation with a single dose of 10 Gy 4 MeV electron beam. At 1 month after irradiation, the hippocampal tissues of the rats were collected. Western blot was used to detect the changes in the expression level of p75NTR protein. Immunofluorescence confocal laser microscopy was performed to observe the variations in the hippocampal neurogenesis. The stereotatic method was adopted for intra-hippocampal injection of AAV-shp75NTR to specifically knock out p75NTR.The relationship between p75NTR and hippocampal neurogenesis was analyzed. Results: Western blot demonstrated that the expression of p75NTR protein was significantly up-regulated by 43.8% after irradiation (P<0.05). Immunofluorescent staining showed that the quantity of BrdU⁺ NeuN⁺ cells in rats was significantly decreased by 81.5% at 1 month after irradiation compared with that in the control group (P<0.01). After the specific knockout of p75NTR, hippocampal neurogenesis was obviously protected. Conclusion p75NTR plays a pivotal role in the irradiation-induced hippocampal neurogenesis impairment.

Objective To explore the optimized ratio of magnesium sulfate and compound polyethylene glycol electric dissolution of two common colon cleansing agent in the preparation of intestinal microscopy, so as to provide references for bowel preparation in clinical colonoscopy treatment. Methods A total of 480 cases of outpatients and inpatients for colonoscopy from March 2016 to March 2017 were selected. All the patients who took magnesium sulfate and compound polyethylene glycol electric dissolution were respectively assigned into four groups according to the dosage and different time of administration, with 60 cases in each group. The effects of bowel preparation and the incidence of adverse effects were compared. Results In the magnesium sulfate groups, there were 53 cases of ClassⅠthe score of bowel cleaning in the group of taking 25% magnesium sulfate 100 ml and water 2 000 ml orally in 1 hour, which was better than the other 3 groups. Hintergroup was 105.654 1 (P<0.01), and Hinterclass was 124.259 9 (P<0.01), and the differences was statistically significant. In the compound polyethylene glycol electric dissolution groups, there were 51 cases of ClassⅠthe score of bowel cleaning in the group of taking 2 boxes of compound polyethylene glycol electric dissolution with water 1 500 ml in 0.5 hour, which was better than the other 3 groups. Hintergrop was 79.280 3, and Hinterclass was 145.504 2, and the difference was statistically significant (P<0.01). There was no statistical significance in the differences of the incidence of adverse effects (H=47.25, 19.50;P>0.05). Conclusions When using magnesium sulfate in the colonoscopy bowel preparation, taking 25% magnesium sulfate 100 ml and warm water 2 000 ml in 1 hour by oral could get the best colon cleaning effects. When using compound polyethylene glycol electric dissolution, the best cleaning effect ratio is 2 boxes of compound polyethylene glycol electric dissolution with water 1 500 ml in 1 hour, which is suitable for popularization and application.

Objective This study is to investigate the changes in the NFATc 4/3 signaling pathway in rat hippocampus after whole brain radiation. Methods A total of 120 one?month?old male Sprague?Dawley rats were randomly divided into four groups to receive whole brain radiation using 4?MeV electron beams with doses of 0( control) ,2,10,and 20 Gy,respectively,in a single fraction. At 6 hours,12 hours,1 day,3 days,1 week,and 2 weeks after radiation,Western blot and real?time PCR were used to evaluate the changes in expression levels of CaN, NFATc 4/3, p?NFATc 4/3, and GSK?3β. Results There were no significant changes in the expression of NFATc 4/3 or p?NFATc 4/3 at 6 and 12 hours after whole brain radiation. At 1 day after radiation,compared with the control group,the expression of p?NFATc 4/3 in the radiation groups was significantly increased in a dose?dependent manner ( 2 Gy:P= 0. 014;10 Gy:P=0. 011;20 Gy:P=0. 000 );however, there was no significant difference in the expression of NFATc 4/3 between the radiation group and the control group. The expression of NFATc 4/3 was significantly decreased in the radiation groups than in the control group at day 3 ( 2 Gy:P=0. 040;10 Gy:P=0. 000;20 Gy:P=0. 000),1 week (2 Gy:P=0. 692;10 Gy:P=0. 032;20 Gy:P=0. 021),and 2 weeks (2 Gy:P=0. 001;10 Gy:P=0. 000;20 Gy:P=0. 000) after radiation,while there was no significant difference in the expression of p?NFATc 4/3 between any two groups. There were no time?or dose?dependent changes in expression of CaN or GSK?3β. Conclusions Ionization radiation has an inhibitory effect on the NFATc 4/3 signaling pathway in rat hippocampus. Combined with our previous results,this study suggests that radiation?induced cognitive dysfunction is associated with the NFATc 4/3 signaling pathway.

Objective To explore the clinical characters,treatment and prognosis of gastrointestinal Dieulafoy lesion in China.Methods Dieulafoy was used as search term,the literatures about Chinese patients with Dieulafoy lesions from January 1998 to October 2016 were retrieved in the Chinese literature library including China National Knowledge Infrastructure,VIP network,Wanfang database and China Biology Medicine disc,and a total of 515 literatures,5 145 patients were enrolled and analyzed.The gender,age,geographical distribution,location of the lesion,treatment and prognosis of the disease were summarized.Results Among the 5 145 patients (male 3 959,female 1 186) with Dieulafoy disease,the ratio of male to female was 3.34∶1.00.The age was from 3 to 95 years,and mean age was 51 years.The lesion location was mainly in stomach (88.82％,4 570/5 145) and second was small intestine (8.28％,426/5 145).In stomach,the lesions were mainly located in gastric corpus,fundus and cardia.The small intestinal Dieulafoy lesions were mainly located in duodenum.The main manifests were sudden hematemesis,melena,and hematochezia.The treatments mainly was endoscopic treatment (72.56％,3 733/5 145),and second was surgery (25.27％,1 300/5 145).Among the5 145 patients withDieulafoy disease,5 099 patients (99.11％) were cured and 46 patients (0.89％) died.The proportions of endoscopic treatment,interventional therapy and first endoscopic treatment within 24 hours in tertiary hospitals were all higher than those of nontertiary (all P＜0.01).The cure rate of tertiary hospitals (99.22％,3 674/3 793) was significantly higher than that of nontertiary hosptials (98.54％,1 421/1 442) (x2 =0.89,P＜0.05) and the mortality was significantly lower than that of nontertiary hospitals (P＜ 0.05).Conclusions The male is more susceptible to Dieulafoy lesion which occurred at any age than the female in China.The predilection sites of Dieulafoy lesion were stomach and duodenum.The primary treatments were endoscopic treatment and surgery,and the disease usually had a good prognosis.

Background:With the deepening of researches on etiology of gastrointestinal bleeding,bleeding caused by pancreatic diseases has been understood better by the clinicians. Upper gastrointestinal bleeding (UGIB)is an uncommon but highly lethal complication of pancreatic diseases. Aims:To analyze the clinical characteristics of UGIB caused by pancreatic diseases for improving the diagnosis and management of this condition. Methods:A total of 22 inpatients who were diagnosed as UGIB caused by pancreatic diseases from Sep. 2010 to Sep. 2016 at Daping Hospital,the Third Military Medical University were recruited and analyzed retrospectively. Results:There were 15 males and 7 females;the disease was more prevalent in young patients than in middle-aged and elderly patients (45. 5% vs. 31. 8% and 22. 7%). The top five causes of bleeding were as follows:stress ulcer related to acute pancreatitis (36. 4%),pancreatic pseudocysts related to chronic pancreatitis (18. 2%),severe acute pancreatitis (13. 6%),post-operative bleeding related to pancreatic surgery (9. 1%)and left-sided portal hypertension (9. 1%). The diagnosis was commonly made by gastroscopy, abdominal contrast-enhanced CT and angiography. Ten patients received medical therapy only,6 were treated by surgical operation,5 by endoscopic hemostasis,and 1 by angioembolization. Hemostasis was achieved in 18 patients (81. 8%), and rebleeding occurred in 4 patients,of which two received medical therapy initially. Two elderly patients died of uncontrollable bleeding and multiple organ failure,respectively. Conclusions:UGIB caused by pancreatic diseases are prone to occur in young and middle-aged males. Pancreatitis and its complications are the major cause of this condition. Medical therapy is ineffective for most of the patients and a multidisciplinary approach of endoscopy,transarterial intervention and surgery is recommended.

Aim To explore the effect of Neu-P11,a novel melatonin agonist with similar function of melatonin,on IOP of acute high IOP animals and the related mechanism.Methods The experiment used the Trendelenburg position(head low feet high position of 80°)to establish acute high IOP model.Rats were placed in the Trendelenburg position and used Tonopen XL contact tonometer to measure IOP(every 5 minutes measured once IOP,and the maximum value in 20 minutes)in 8 :00～9 :00 am.And then,thirty Sprague-Dawley rats(8 week-old)were divided into five groups: normal IOP+normal saline,high IOP+normal saline,high IOP+10 mg·kg-1 Mel,high IOP+20 mg·kg-1 Neu-P11,high IOP+50 mg·kg-1 Neu-P11.Put in a flat to rest 2 h,animals were placed in Trendelenburg position again and then,IOP was measured every hour in the flat by 6 hours.After excessive sodium pentobarbital administration continuous for 1 week,the serum was collected and stored for subsequent detection at the end of the experiment.The level of MDA,SOD and GSH-Px enzyme activity of the rat serum was tested by kit accordingly.HE staining method was used to identify the SD rat retinal morphological changes.Results Trendelenburg position could induce IOP of model group rats,which was increased by 202.9％(P<0.01)and the content of MDA,reduced the activity of SOD and GSH-Px enzyme,retinal thickening was observed and its level was not clear.Neu-P11/Mel could significantly improve oxidative stress level and retinal edema in rats.Conclusion Neu-P11 could reduce IOP of the acute high IOP animals,which might be involved in the lower level of oxidative stress in the body.

Objective To explore the effects of various radiation doses on the NFAT3/c4 signaling pathway and the improvement effect of exogenous brain-derived neurotrophic factor(BDNF)on this pathway. Methods Four groups of one-month-old Sprague-Dawley rats received radiation doses of 0,2,10,and 20 Gy, respectively, in a single radiation. At three days after radiation, exogenous BDNF was injected stereotaxically into the bilateral hippocampus. Western blotting and RT-PCR were used to assess the levels of NFAT3/c4-related proteins in the hippocampus. Results The results of Western blotting and RT-PCR showed that the level of NFAT3/c4 was reduced in a dose-and time-dependent manner after ionizing radiation. Compared with the radiation alone group,the ionizing radiation plus BDNF group had significantly increased levels of NFAT3/c4 and CaN with increases in radiation dose and time. Conclusions Whole brain radiotherapy inhibits the CaN/NFAT3/c4 signaling pathway. Exogenous BDNF can promote the NFAT-dependent transcription and then improve the cognitive function.