OBJECTIVE To investigate the effects of borneol on pharmacodynamic and pharmacokinetic effects of Corydalis saxicola total alkaloids in depression model rats. METHODS Thirty male SD rats were divided into blank control group， negative control group， positive control group （fluoxetine 10 mg/kg， i.g.）， single drug group （C. saxicola total alkaloids 210 mg/kg， i.g.） and combined drug group （C. saxicola total alkaloids 210 mg/kg+borneol 50 mg/kg， i.g.） according to the random number table method， with 6 rats in each group. By lipopolysaccharide （LPS） induction modeling， except blank control group （no model and no administration） received intraperitoneal injection of the same amount of normal saline， the rats in the other groups were intraperitoneally injected with LPS once a day to establish a rat model of depression. After 1 week of modeling， each administration group was given relevant drug intragastrically according to the corresponding dose， and blank control group and negative control group （without drug treatment） were administered intragastrically with an equal volume of solvent to dissolve the drug； continued modeling while administering the drug. After two weeks of continuous administration， the effects of C. saxicola total alkaloids versus the combination of C. saxicola total alkaloids and borneol on the behavior of depressed rats were tested by behavioral experiments； the levels of tumor necrosis factor-α， interleukin-1β and interleukin-6 in rats were determined； the histopathological changes of the hippocampus of rats were observed. Blood sample was collected from the orbit at different time points after administration on the 15th day， and the upper plasma was obtained. Ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry was established for the simultaneous determination of dehydrocarvedine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in rat plasma. The average plasma concentration-time curve was depicted， the area under the curve （AUC） was calculated， and the pharmacokinetic parameters were analyzed by DAS 3.2.2 software. RESULTS Compared with blank control group， the negative control group had a decrease in body mass and sugar water preference rate， a decrease in the total distance of open field， a prolonged swimming immobility time， and a increased in the expression of inflammatory factors in serum （P＜0.05）； compared with negative control group, the single drug group and the combined drug group increased the preference rate of sugar water， increased the total distance of open field， shortened the time of swimming immobility， and decreased the expression of inflammatory factors in serum （P＜0.05）. There was no significant difference in the above indicators between the single drug group and the combined drug group in rats （P＞0.05）. Pharmacokinetic results showed that compared with single drug group， AUC0-t of coptisine， AUC0-t， AUC0-∞， tmax and cmax of jatrorrhizine， AUC0-t， AUC0-∞， t1/2 and cmax of berberrubine， and AUC0-t of epiberberine， cmax of dehydrocarvedine， cmax of palmatine were significantly increased in combined drug group， but there was no significant difference， indicating that borneol didn’t have a significant effect on the efficacy of Corydalis saxicola nigra at this dose. CONCLUSIONS Both C. saxicola total alkaloids alone and in combination with borneol can improve depression-like behavior in depression model rats， reduce serum inflammatory cytokine levels， and protect hippocampal neurons. Compared with the use of Corydalis saxicola base alone， the combination with borneol do not show significant pharmacodynamic differences， bu can improve the absorption of coptisine， jatrorrhizine in model rats.

Objective:To develop a deep learning method to predict the anatomical images of nasopharyngeal carcinoma patients during the treatment course, which could detect the anatomical variation for specific patients in advance.Methods:Imaging data including planning CT (pCT) and cone-beam CT (CBCT) for each fraction of 230 patients with T 3-T 4 staging nasopharyngeal carcinoma who treated in Cancer Hospital Chinese Academy of Medical Sciences from January 1, 2020 to December 31, 2022 were collected. The anatomical images of week k+1 were predicted using a 3D Unet model with inputs of pCT, CBCT on days 1-3, and CBCT of weeks 2- k. In this experiment, we trained four models to predict anatomical images of weeks 3-6, respectively. The nasopharynx gross tumor volume (GTV nx) and bilateral parotid glands were delineated on the predicted and real images (ground truth). The performance of models was evaluated by the consistence of the delineation between the predicted and ground truth images. Results:The proposed method could predict the anatomical images over the radiotherapy course. The contours of interest in the predicted image were consistent with those in the real image, with Dice similarity coefficient of 0.96, 0.90, 0.92, mean Hausdorff distance of 3.28, 4.18 and 3.86 mm, and mean distance to agreement of 0.37, 0.70, and 0.60 mm, for GTV nx, left parotid, and right parotid, respectively. Conclusion:This deep learning method is an accurate and feasible tool for predicting the patient's anatomical images, which contributes to predicting and preparing treatment strategy in advance and achieving individualized treatment.

OBJECTIVE To investigate the mechanisms by which Pinggan Yishen Decoction(PGYSD)contributes to alleviating target organ damage in spontaneously hypertensive rats.METHODS The chemical components of PGYSD were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)and were analyzed by target a-nalysis and functional enrichment combined with network pharmacology methods to predict the potential mechanism of PGYSD in trea-ting hypertension and its target organ damage.Spontaneously hypertensive rats were randomly divided into the model group,low-dose PGYSD group(2 g·kg-1),high-dose PGYSD group(5 g·kg-1),and valsartan group(7.2 mg·kg-1),with 6 rats in each group.Wistar-Kyoto rats were used as the control group,and the control group and the model group were gavaged with normal saline for 8 consecutive weeks.HE and Masson staining were used to observe the pathological damage and fibrosis degree of rat heart and tho-racic aorta.Immunohistochemical staining and Western blot were used to detect the expression level of EGFR in the heart,liver and kidney of rats.Immunofluorescence staining was used to detect the co-localization of EGFR and EEA1 in the heart,liver and kidney of rats.RESULTS Twenty-six components of PGYSD were detected by UPLC-Q-TOF/MS.Network pharmacology revealed that EG-FR,PIK3R1 and EP300 may be key therapeutic targets of action of PGYSD for the treatment of hypertension and its target organ dam-age,and that the treatment of hypertension and its target organ damage by PGYSD may be closely related to EGFR tyrosine kinase in-hibitor resistance,lipids and atherosclerosis and HIF-1 signaling pathway.The high-dose group of PGYSD significantly reduced sys-tolic blood pressure and mean blood pressure in rats(P<0.05,P<0.01),attenuated pathological damage and fibrosis in the heart and thoracic aorta(P<0.01,P<0.001),significantly reduced the expression level of EGFR in the liver and kidney of rats(P<0.01),and treated fibrosis in liver and kidney,reduced the co-localization of EGFR and EEA1 in the kidney of rats(P<0.001),attenuated fibro-sis in kidney.CONCLUSION The paper integrates UPLC-Q-TOF/MS,network pharmacology and spontaneously hypertensive rat model and preliminarily explores the effect mechanism of PGYSD in the treatment of hypertension and its target organ damage,provi-ding a scientific basis for further mechanism research and clinical application of PGYSD in the treatment of hypertension.

ObjectiveTo investigate the effect of total alkaloids of Corydalis saxicola on a rat model of lipopolysaccharide（LPS）-induced depression， as well as the pharmacokinetic characteristics of 8 of its major components. MethodTwenty-four male SD rats were randomly divided into normal group， model group， fluoxetine group（10 mg·kg^-1） and total alkaloids of C. saxicola group（210 mg·kg^-1）， with 6 rats in each group. In addition to the normal group， the rats were injected intraperitoneally with LPS to establish the inflammation model of depression， and the drug administration was started 1 week after modeling， and the administration groups were gavaged according to the corresponding dose， and the normal and model groups were intragastric administration with equal volume of distilled water， and the administration was performed along with the modeling. After two weeks of continuous administration， the effect of total alkaloids of C. saxicola on the behavior of depressed rats were tested by sucrose preference， forced swimming and open field experiments， the levels of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum of rats were determined by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of rat hippocampus were observed by hematoxylin-eosin（HE） staining. After the last administration， blood was collected from orbit according to the set time， and ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS） was established to simultaneously detect the concentrations of dehydrocavidine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in plasma， and drug-time curves were drawn. The pharmacokinetic parameters were analyzed by DAS 2.0 software. ResultCompared with the normal group， the model group exhibited a decrease in sucrose preference rate， total distance traveled in the open field， as well as an increase in swimming immobility time and serum inflammatory factor expression（P<0.01）. In contrast， compared with the model group， rats in each administration group showed an increase in sucrose preference rate and total distance traveled in the open field， a decrease in swimming immobility time， and a reduction in serum inflammatory factor expression（P<0.05， P<0.01）. Additionally， HE staining results revealed that neurons in the hippocampus of rats from the model group were characterized by loss， disorganization and residual vacuoles， whereas those from the total alkaloids of C.saxicola group displayed an increase in number with orderly arrangement and clear cytoplasm. Pharmacokinetic results showed that the time to peak（t_max） and half-life（t_1/2） of the 8 active ingredients were 0.19-2.06 h and 3.71-8.70 h after continuous administration of total alkaloids of C. saxicola. Among them， the area under the curve（AUC_0-∞） of tetrahydropalmatine was the highest and the t_1/2 was the shortest， and the AUC_0-∞ of coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine were low. The curves of dehydrocavidine， coptisine， palmatine， berberine and epiberberine showed obvious double peak phenomenon. ConclusionTotal alkaloids of C. saxicola can improve the depression-like behavior of rats， inhibit the expression of inflammatory factors in serum， improve the pathological injury of hippocampus， and has the antidepressant effect. Meanwhile， the effective site is absorbed quickly and eliminated slowly in the depressed model rats， and the efficacy is maintained for a long time.

ObjectiveTo investigate the pharmacodynamics， pharmacokinetics and brain distribution of seven main components of Jiaotaiwan alone and Jiaotaiwan combined with borneol in lipopolysaccharide（LPS）-induced depression rats. MethodRats were randomly divided into the control group， model group， fluoxetine group（10 mg·kg^-1）， Jiaotaiwan group（1.5 g·kg^-1） and combination group（1.5 g·kg^-1 of Jiaotaiwan+0.05 g·kg^-1 of borneol）， with 8 rats in each group. Except for the control group， the depression model was established by intraperitoneal injection of LPS for 7 consecutive days， and each group was given the corresponding drugs or the same volume of pure water by gavage for 14 consecutive days. The behavioral indicators and levels of serum inflammatory factors［interleukin-1β（IL-1β）， IL-6 and tumor necrosis factor-α（TNF-α）］ of rats in each group were compared. The morphological changes of hippocampal neurons were observed by hematoxylin-eosin（HE） and Nissl staining. After the behavioral tests of sucrose preference， open field and forced swimming were completed， blood samples were collected from Jiaotaiwan group and combination group at the set time points after gavage， the contents of seven components in plasma were determined by ultra performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）， and the pharmacokinetic parameters of each component were analyzed by DAS 3.2.2. Brains were rapidly removed on ice after blood collection was completed， and UPLC-QqQ-MS/MS was used to compare the content changes of the 7 components in brain tissue. ResultCompared with the control group， rats in the model group showed decreased sucrose preference rate and total distance of open field， prolonged swimming immobility time， and increased expression of inflammatory factors in serum（P<0.01）. Compared with the model group， the sucrose preference rate and total distance of open field were increased， and the swimming immobility time was shortened in the rats of each administration group， and the expression of inflammatory factors in serum was decreased in rats from Jiaotaiwan group and combination group（P<0.05， P<0.01）. The results of HE and Nissl staining showed that Jiaotaiwan group and combination group had a certain protective effect on hippocampal neurons. The pharmacokinetic results showed that compared with Jiaotaiwan group， the area under the curve（AUC_0-t， AUC_0-∞）， peak concentration（C_max） and the average steady-state plasma concentration（C_av） of berberine and epiberberine in the combination group were increased（P<0.05， P<0.01）， AUC_0-t， AUC_0-∞， mean residence time（MRT_0-∞） and C_av of coptisine were significantly increased（P<0.05， P<0.01）， C_max of jatrorrhizine increased significantly（P<0.05）， but the pharmacokinetic changes of the seven alkaloids were consistent. The results of brain tissue distribution showed that compared with Jiaotaiwan group， the contents of jatrorrhizine， epiberberine， coptisine， palmatine and berberine in the brain tissue of combination group were increased（P<0.05， P<0.01）， the content of magnoflorine increased and that of berberrubine decreased， but the difference was not statistically significant. ConclusionJiaotaiwan alone or combined with borneol can improve the depression-like behavior of rats， reduce the levels of serum inflammatory factors， improve the pathological damage of hippocampus， and have antidepressant effect. Compared with Jiaotaiwan alone， the combination of Jiaotaiwan and borneol can increase the exposure of multiple active components of Jiaotaiwan in the plasma and brain tissue of rats， improve its bioavailability， promote its absorption， and improve the brain targeting of the drug， which is more conducive to the antidepressant effect of Jiaotaiwan.

Objective:To evaluate the feasibility of using MRI-only simulation images for dose calculation of both photon and proton radiotherapy for nasopharyngeal carcinoma cases.Methods:T 1-weighted MRI images and CT images of 100 patients with nasopharyngeal carcinoma treated with radiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from January 2020 to December 2021 were retrospectively analyzed. MRI images were converted to generate pseudo-CT images by using deep learning network models. The training set, validation set and test set included 70 cases, 10 cases and 20 cases, respectively. Convolutional neural network (CNN) and cycle-consistent generative adversarial neural network (CycleGAN) were exploited. Quantitative assessment of image quality was conducted by using mean absolute error (MAE) and structural similarity (SSIM), etc. Dose assessment was performed by using 3D-gamma pass rate and dose-volume histogram (DVH). The quality of pseudo-CT images generated was statistically analyzed by Wilcoxon signed-rank test. Results:The MAE of the CNN and CycleGAN was (91.99±19.98) HU and (108.30±20.54) HU, and the SSIM was 0.97±0.01 and 0.96±0.01, respectively. In terms of dosimetry, the accuracy of pseudo-CT for photon dose calculation was higher than that of the proton plan. For CNN, the gamma pass rate (3 mm/3%) of the photon radiotherapy plan was 99.90%±0.13%. For CycleGAN, the value was 99.87%±0.34%. The gamma pass rates of proton radiotherapy plans were 98.65%±0.64% (CNN, 3 mm/3%) and 97.69%±0.86% (CycleGAN, 3 mm/3%). For DVH, the dose calculation accuracy in the photon plan of pseudo-CT was better than that of the proton plan.Conclusions:The deep learning-based model generated accurate pseudo-CT images from MR images. Most dosimetric differences were within clinically acceptable criteria for photon and proton radiotherapy, demonstrating the feasibility of an MRI-only workflow for radiotherapy of nasopharyngeal cancer. However, compared with the raw CT images, the error of the CT value in the nasal cavity of the pseudo-CT images was relatively large and special attention should be paid during clinical application.

{L-End}Objective To investigate the effect of motorcycle exhaust (ME) on the level of oxidative stress in different parts of respiratory tract epithelial cells. {L-End}Methods BEAS-2B and A549 cells in logarithmic growth phase were randomly divided into control group, low- and high-dose groups. The two kinds of cells growing on the membrane of Transwell inserts were treated with air-liquid interface (ALI) exposure technique for 60 minutes. The cells in the low- and high- dose groups were treated with diluted gas with the volume ratio of ME to clean air of 1∶20 and 1∶10, respectively, while the cells in the control group were treated with clean air. Cells were collected to detect their relative survival rate using CCK-8 method after exposure. And the levels of malondialdehyde, glutathione and the activity of superoxide dismutase (SOD) of the cells were detected using colorimetry. {L-End}Results The ME exposure dose affected the relative survival rate of cells (P<0.01), which showed a downward trend with the increasing ME exposure doses (all P<0.05). However, there was no significant difference in the main effect of cell types and the interaction effect of ME exposure dose and cell type (all P>0.05). There was a significant interaction between ME exposure dose and cell type in the level of glutathione and the activity of SOD (all P<0.01), and the level of malondialdehyde was a significant main effect of cell type (P<0.01). There was no significant difference in the glutathione level and SOD activity between the low-dose group and the control group (all P>0.05), while the glutathione level and SOD activity in high-dose group were higher than those in the control group and low-dose group in BEAS-2B cells (all P<0.05). The glutathione level decreased with increasing ME exposure dose in A549 cells (all P<0.05). Compared with the control group, the low-dose group had a significantly higher activity of SOD (P<0.05) in A549 cells. The SOD activity of A549 cells in high-dose group was lower than those in control group and low-dose group (all P<0.05). The level of malondialdehyde in A549 cells was higher than those in BEAS-2B cells(P<0.05). {L-End}Conclusion ME exposure can lead to changes in the production of oxidative stress biomarkers in respiratory tract epithelial cells. The oxidative stress response induced by ME exposure varies among respiratory tract epithelial cells from different regions.

At present, there are still some problems in the standardized residency training. Some standardized training bases often regard the resident trainees as ordinary practitioners, and devote their time and energy to the daily medical procedural work without giving enough training and teaching, ignoring the basic skills training of resident trainees. Therefore, this study constructed an active knowledge push system based on business scenarios. The system mainly includes three parts: sensitive operation identification layer, knowledge index layer and resource push layer in order to cultivate the norms of diagnosis and treatment of standardized training students and reasonably solve the problem of inconvenient resource acquisition in clinical work. Through the preliminary application, it was found that the system has effectively improved the mini-clinical evaluation exercise (Mini-CEX) score of the trainees and achieved good results.

Objective:To determine the predictive value of atherogenic index of plasma (AIP) on the long-term prognosis of patients with coronary artery disease (CAD).Methods:A total of 2 500 patients with coronary heart disease who underwent coronary angiography in Affiliated Hospital of Jining Medical University from May 2013 to November 2015 were retrospectively analyzed. According to the AIP value, the subjects were divided into low AIP group (AIP<0.06) and high AIP group (AIP≥0.06). The incidence of major adverse cardiovascular events (MACE) was compared between the two groups. Kaplan-meier method was used to evaluate the MACE-free survival rate, and multivariate Cox survival analysis was used to evaluate the independent predictors of MACE.Results:A total of 2 427 patients were followed up, with a follow-up rate of 97.08% and a median follow-up time of 4.29 years. There were 1 123 cases in the low AIP group and 1 304 cases in the high AIP group, among which 624 patients (25.7%) had MACE. The total incidence of MACE in the high AIP group was higher than that in the low AIP group ( HR=1.43, 95% CI: 1.22-1.68, P<0.01). Kaplan-meier curves showed that the MACE-free survival rate was significantly lower in the high AIP group ( P<0.01). After adjusting for multiple confounding factors, AIP was still associated with the prognosis of CHD patients. Increased AIP (≥0.06) was an independent predictor of MACE in CHD patients within 4 years ( HR=1.34, 95% CI: 1.14-1.58, P<0.01). Conclusions:AIP (≥0.06) was an independent predictor of MACE occurrence in patients with CAD within 4 years. AIP has a certain value in the long-term prognosis of patients with CAD.

Objective:Using lasso regression analysis to screen out the blood lipid indexes closely related to coronary heart diseaseMethods:The clinical data of 3 062 patients with coronary heart disease who were hospitalized in the Department of Cardiology, Affiliated Hospital of Jining Medical College from May 2013 to November 2015 were retrospectively analyzed.They were divided into control group ( n=2 427) and coronary angiography group ( n=635). R language was used for statistical analysis.Multiple logistic regression models were established for indicators of blood lipid related to CAD, and their multicollinearity severity was assessed.LASSO regression was used to screen out the representative lipid parameters in the CAD prediction model. Results:A total of 3 062 patients were enrolled, including 2 427 patients in coronary heart disease group and 635 patients in control group.The inclusion of lipid parameters into multiple logistic regression model leads to serious multicollinearity.Stepwise regression can only partially reduce multicollinearity severity, while LASSO regression model significantly reduces multicollinearity severity.Low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) were found to be the representative lipid indexes for predicting coronary heart disease by LASSO regression analysis.Conclusion:LASSO regression has advantages in processing multicollinearity data.LASSO regression showed that LDL-C, HDL-C and non-HDL-C were representative lipid indicators for predicting coronary heart disease..