Objective To investigate the effect of midazolam on neuronal damage in ischemic stroke （IS） rats and its regulatory effect on PTEN-induced putative kinase 1 （PINK1）/E3 ubiquitin ligase （PARKIN） signaling pathway. Methods An IS rat model was established using arterial occlusion method. The rats with successful model were randomly divided into IS group, drug-low, medium, high-dose （drug-L, M, H, 30, 60, 90 mg/kg midazolam） groups, drug-H+autophagy inhibitor 3-MA group （90 mg/kg midazolam+30 mg/kg 3-MA）, and rats with only isolated blood vessels were used as sham surgery groups. Each group received corresponding doses of drugs or physiological saline intervention, and the neurological function scoring, brain histopathology, neuronal apoptosis, ultrastructure, and expression of PINK1, PARKIN, microtubule-associated protein 1 light chain 3 （LC3）, and P62 protein in mitochondria were detected. Results Compared with the IS group, the pathological damage of the drug-L group, drug-M group, and drug-H group was improved, and autophagosomes showed an increasing trend, the expression of PINK1, PARKIN, and LC3 proteins increased, the neurological function score, neuronal apoptosis rate, and P62 protein obviously decreased in a dose-dependent manner （P<0.01 or P<0.001）; compared with the drug-H group, the pathological damage in the drug-H+3-MA group increased and autophagosomes decreased, the expression of PINK1, PARKIN, and LC3 proteins decreased, the neurological function score, neuronal apoptosis rate, and P62 protein obviously increased （P<0.001）. Conclusion Midazolam induced mitochondrial autophagy in IS rats by activating the PINK1/PARKIN signaling pathway, neuronal apoptosis was reduced and neuronal damage were improved in IS rats.

OBJECTIVE To establish a content determination method for multiple components in Sophora flavescens from different origins and to evaluate its quality by combining with chemometrics. METHODS Thirteen batches （No. K1-K13） of S. flavescens from different origins were selected as test samples. A high-performance liquid chromatography-tandem triple quadrupole mass spectrometry （HPLC-MS/MS） method was established to determine the contents of 12 components， including matrine， oxymatrine， betaine， cytisine， N-methylcytisine， sophoridine， genistein， sophoricoside， sophorone， formononetin， sophorolone Ⅰ and norkurarinone in S. flavescens. Chromatographic separation was performed on a Shim-pack GIST-HP C18 column with a mobile phase consisting of methanol （A） and water containing 0.1% formic acid （B）， using gradient elution at a flow rate of 0.25 mL/min， column temperature of 35 ℃， and an injection volume of 3 μL. Mass spectrometry was conducted using an electrospray ionization source with positive and negative ion scanning. Data were collected in segments using the multiple reaction monitoring mode. Technique for order preference by similarity to ideal solution （TOPSIS） and grey relational analysis （GRA）methods were employed to compare and comprehensively evaluate the 13 batches of S. flavescens from different origins. RESULTS The methodological validation for the content determination met the relevant regulatory requirements. The contents of the 12 components were 490.66-1 231.00， 11 088.10- 18 021.50， 7.91-25.38， 903.97-1 713.64， 336.08-1 485.54，1 065.33-2 075.50， 27.52-71.80， 109.36-517.83， 6 034.55-10 632.73， 21.26-145.35， 814.84-1 911.32， 1 040.87-3 446.37 μg/g）， respectively. TOPSIS results showed that the top 7 samples in Euclidean distance ranking were K6， K12， K11， K3， K5， K10， K13. The GRA results showed that the top 7 samples in the relative correlation ranking were K12， K11， K10， K6， K13， K5， K3. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate， highly sensitive， stable and reliable. Combined with chemometrics methods， it can be used for the quality control and evaluation of S. flavescens. The comprehensive quality of samples K3， K5， K6（ from Hebei）， K10（ from Sichuan）， K11-K13（ from Shanxi）， etc. is relatively superior.

Objective:To establish a mice model that is more in line with the human immunocompromised state,and to inves-tigate the regulatory effect of Rosa laevigata Michx.,probiotics and their combination on their immune function.Methods:Immunosup-pressive model of mice was established by using cyclophosphamide with different dosage,time and end point,and compared with im-munosuppressive model induced by hydrocortisone and cyclosporine A,immunosuppressive model of mice was established by injecting 25 mg/kg cyclophosphamide 7 times every other day,without recovery period;changes in the proportion of lymphocytes in spleen(CD4+T cells,CD8+T cells,CD19+B cells)were analyzed by flow cytometry;qRT-PCR was used to detect expression levels of inflam-matory factors(IL-1β and IL-6)mRNA in spleen.Results:After continuous injection of 80 mg/kg cyclophosphamide for 3 days,the thymus was atrophied,the spleen was significantly swelling,proportion of immune cells CD4+T cells,CD8+T cells and CD19+B cells in spleen were significantly decreased,while mRNA expressions of IL-1β and IL-6 were up-regulated.After 7 injections of 25 mg/kg cyclophosphamide every other day,the thymus and the spleen were significantly atrophied,proportion of CD4+T cells and CD8+T cells in spleen showed an increasing trend,and mRNA expressions of IL-1β and IL-6 were up-regulated;after 1 week or 2 weeks recovery period from cyclophosphamide injection,weight and index of immune organs,proportion of spleen lymphocytes and mRNA expres-sions of inflammatory cytokines in spleen were significantly reversed;Rosa laevigata Michx.combined with probiotics could signifi-cantly reverse the up-regulation of CD4+T cells and inflammatory factor IL-1β caused by cyclophosphamide.Conclusion:In this study,an immunocompromised mice model has been established with 7 injections of 25 mg/kg cyclophosphamide every other day and without recovery period.And a certain positive immunomodulatory effect of the combination of Rosa laevigata Michx.and probiotics has been found.

Objective:To explore the potential relationship between sugar metabolism,acid production and cariogenicity of Prevotella denticola.Methods:Morphological features of Prevotella denticola were observed and respectively cultured under incubation conditions with and without sugar and at different pH values.The growth characteristics of Prevotella denticola were detected by UV-Vis spectro-photometer and pH meter,the organic acid content in the culture supernatants of the cultures was detected by HPLC.Dentin slices were divided into control group,phosphoric acid group and the Prevotella denticola group and cultured in the corresponding mediu for 1 and 2 weeks respectively,the degree of demineralization of the samples was examined SEM and VHM.Results:Prevotella denticola fermen-ted sucrose and glucose,produced acids with its final pH values as low as 4.7,Succinic acid and acetic acid were its main metabolites.Prevotella denticola was moderately acid-tolerant.Furthermore,Prevotella denticola was able to cause dentin demineralization,and the Vickers hardness value of dentin samples in the Prevotella denticola group was significantly decreased compared with the control group(P＜0.05).Conclusion:The cariogenic capacity of Prevotella denticola may be related to its sugar metabolism and acid production.

Objective:To assess the performance of machine learning(ML),and integrate the clinical parameters with coronary artery calcium(CAC)score of computed tomography(CT)and quantification of automated epicardial adipose tissue(EAT),so as to predict the long-term risk of myocardial infarction(MI)and cardiogenic death in asymptomatic patients.Methods:A total of 1 058 subjects with cardiovascular risk factors and without symptoms of coronary heart disease who underwent physical examination at the Fifth Medical Center of Chinese PLA General Hospital from January 2013 to October 2015 were selected as this study subjects.A long-term follow-up was conducted on them after CAC score.EAT volume and density were quantified using a fully automated deep learning method.ML extreme gradient boosting was trained by using clinical data,risk score of atherosclerotic cardiovascular disease,CAC score and automated EAT measure,and the repeated 10-fold cross validation was used to verify the model.Results:During the 8-year follow-up period,61 cases of 1 058 subjects occurred events of MI and(or)cardiac death.The area under curve(AUC)value of ML was significantly higher than that of the atherosclerotic cardiovascular disease(ASCVD)risk and the predicting events of CAC score(ML:0.82,ASCVD:0.77,CAC:0.77).Compared with ML with only clinical variable,machine learning based on ASCVD,CAC and EAT had more predictive ability for MI and cardiac death[AUC 0.82(95%CI:77-87)vs.0.78(95%CI:0.72-0.84),P=0.02].The survival rate of subjects with high ML scores had a greater decline degree with the increasing of time,therefore,the subjects with higher ML scores were more likely to experience events.Conclusion:ML,which integrated clinical and quantitative imaging variables,can provide long-term risk prediction for patients with cardiovascular risk factors.

Objective:To evaluate the therapeutic effects of Yufu ointment for acute radiation-induced skin injury. Methods:We enrolled a total of 104 patients with malignant tumors who developed acute skin injury of grade 2-3 during or after the first course of radiotherapy from June 2019 to February 2023. The observation group ( n=53) and control group ( n=51) received external application of Yufu ointment and Shirun Shaoshang ointment, respectively. We recorded the changes in the grade of skin injury and associated symptoms (such as pain, itching, and burning sensation) and healing speed and time for the two groups. Results:A total of 102 patients completed the study, with 53 cases in the observation group and 49 cases in the control group. The incidence rate of moisture skin lesions in the observation group was significantly lower than that in the control group (62.26% vs. 83.67%, P<0.05). The healing speed of moisture skin ulcerations was significantly faster in the observation group than in the control group (1.67 cm 2/d vs. 0.55 cm 2/d, P<0.05). The observation group had a significantly shorter time to skin injury healing than the control group (10.40 d vs. 14.41 d, P<0.05), significantly different for skin injury of grade 2 (10.21 d vs. 17.57 d, P<0.05) but not for skin injury of grades 2.5 and 3 ( P>0.05). Regarding clinical symptoms, both groups experienced significant reductions in pain and burning sensation scores after treatment ( P<0.05); the grade of itching was significantly decreased for the observation group ( P<0.05), but had no significant change for the control group after treatment ( P>0.05). Conclusions:Yufu ointment can significantly alleviate secondary damage for patients with acute radiation-induced skin injury, by accelerating the healing process and relieving symptoms such as pain, itching, and burning sensation with good tolerability, which deserves further promotion.

90Y microspheres radioembolization therapy is an emerging interventional technique used for the treatment and palliative care of intermediate and advanced liver cancer, which was registered by National Medical Products Administration for imported drugs in 2022. In order to improve the tumor response rate and reduce toxic effects, the dose assessment for the tumor and healthy tissues is implemented throughout treatment. The efficiency and accuracy of estimation method are the keys to improving the therapeutic effect. This article investigated and summarized six evaluation method and their latest progress, discussed the unique advantages and applicable scenarios of each methods, and explored the possible challenges faced in clinical applications. This study would support the development and standardization of dose prediction and evaluation in radioembolization with 90Y microspheres.

OBJECTIVE To investigate the effects of dexmedetomidine （DEX）-assisted general anesthesia on hemodynamics and cognitive function in elderly patients undergoing painless enteroscopy. METHODS From July 2020 to February 2022， 180 elderly patients undergoing painless enteroscopy in the outpatient operating room of the Second People’s Hospital of Jiaozuo were selected and divided into a control group （n＝90） and an observation group （n＝90） according to the random number table method. The control group was given routine general anesthesia （induced with sufentanil and propofol anesthesia， maintained with propofol anesthesia）， while the observation group was given DEX-assisted general anesthesia after preoperative preparation. The hemodynamic indexes [mean arterial pressure （MAP）， heart rate （HR）]， dosage of general anesthesia， awakening time， cognitive function [minimized mental status examination （MMSE）]， and the incidence of adverse drug reactions were compared between the two groups. RESULTS There was no significant difference in various indicators before anesthesia （T0） between 2 groups （P＞ 0.05）. Compared with T0， MAP and HR of the two groups were reduced significantly 10 minutes after anesthesia （T1）， at the time of enteroscope reaching the ileum and cecum （T2）， enteroscope withdrawal after the examination （T3）， and 10 minutes after surgery （T4）； but MAP and HR of the observation group at T1， T2， T3， and T4 were all higher than those of the control group （P＜0.05）. Compared with the control group， the dosage of general anesthesia and the recovery time in the observation group were significantly reduced or shortened， the MMSE scores at 1， 2 and 3 days after the operation were significantly increased， while the incidence of cognitive dysfunction and adverse reactions were significantly reduced （P＜0.05）. CONCLUSIONS DEX can effectively improve the hemodynamics and cognitive function of elderly patients undergoing painless enteroscopy， which is beneficial to reduce the dosage of general anesthesia， shorten recovery time， and has better safety.

Objective To compare the efficacy of three different methods in the prevention of adhesion after the HEOS system for different degrees of intrauterine adhesions.Methods 284 patients with mild,moderate and severe intrauterine adhesions,who were treated with the HEOS system,were divided into three groups,the intrauterine device with sodium hyaluronate gel was placed in Group A,Foley water capsule tube with sodium hyaluronate gel was placed in Group B,and sodium hyaluronate gel was placed in Group C only.The recovery of uterine adhesion,improvement of menstruation,endometrial thickness,and adverse reactions were compared among the three groups.Results The mild intrauterine adhesions group showed statistical differences among the three groups(P<0.05).Group A had a higher menstrual improvement rate than Group C(P<0.017),and there was no significant difference in other therapeutic indicators(P>0.017).However,the adverse reaction rate in Group A was also higher than that in Group C(P<0.017).In the moderate intrauterine group,there was a significant difference in the improvement rate of intrauterine adhesions between Group B and the other two groups(P<0.017).Group A and B were higher than Group C in terms of menstrual status,endometrial thickness,and adverse reactions(P<0.017).In severe intrauterine adhesions,Group A had higher efficacy indicators than other groups(P<0.017).Conclusions The curative effect index and adverse reaction rate were analyzed,after operation.For the light,moderate,and severe intrauterine adhesions,sodium hyaluronate gel,Foley water capsule tube with sodium hyaluronate gel,and intrauterine device with sodium hyaluronate gel were the best choice for adhesion.Individual and hierarchical management can achieve good clinical effects,which is worth popularizing.

Objective:To develop and verify a nomogram to predict disease-free survival(DFS)and overall survival(OS)for patients undergoing cervical cancer surgery,which may provide reference for evaluating the prognosis of cervical cancer patients undergoing surgery.Methods:The clinical,pathological and follow-up data of patients who underwent radical operation for cervical cancer in Xijing Hospital,Air Force Medical University from March 2013 to October 2018 were analyzed retrospectively.Based on Cox regression analysis,Bayesian Informa-tion Criterion(BIC)backward stepwise selection method and R square screening variables,Net Reclassification Index(NRI)and Integrated Discrimination Improvement(IDI)were used to compare the predictive efficiency of the model,and a nomogram with better predictive efficiency was selected.The consistency index(C-index)and the receiver operating characteristic curve(ROC)were used to test the efficiency of the nomogram.Results:A total of 950 patients with cervical cancer were enrolled in this study.The risk factors for constructing the DFS nomogram were FIGO stage(2018),parametrium invasion,invasion depth,and maximum tumor diameter.The C-index for DFS in the training cohort and the verification cohort were 0.754 and 0.720,respectively.The area under ROC of the training cohort for 1-,3-and 5-years was 0.74(95%CI 0.65-0.82),0.77(95%CI 0.71-0.83)and 0.79(95%CI0.74-0.85),and the areas under ROC of verification cohort 1-,3-and 5-years were 0.72(95%CI 0.58-0.87),0.75(95%CI 0.64-0.86)and 0.72(95%CI 0.61-0.84),respectively.The risk factors for con-structing the OS nomogram were FIGO stage(2018),histological type,LVSI,parametrium invasion,surgical mar-gin,and invasion depth.The C-index for OS in the training cohort and the verification cohort were 0.737 and 0.759,respectively.The area under ROC of the 3-and 5-year training cohort were 0.76(95%CI 0.69-0.83)and 0.78(95%CI 0.72-0.84),and the areas under ROC of verification cohort 3-and 5-years were 0.76(95%CI 0.65-0.87)and 0.79(95%CI 0.69-0.88),respectively.Conclusions:This study is based on real-world big data to construct nomogram of DFS for 1,3,and 5 years and OS for 3,and 5 years for cervical cancer,which have ideal predictive effects and help clinical physicians correctly evaluate the prognosis of cervical cancer surgery patients.It provides strong reference basis for diagnosis,treatment,and prognosis evaluation.