ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

Emergence agitation （EA） is a common complication after general anesthesia， especially in children and adolescents. Remifentanil， as a short-acting μ-receptor agonist， has become an important drug for the prevention and treatment of EA due to its rapid recovery and low risk of respiratory depression. This article reviews the mechanism of action and clinical research progress of remifentanil in the prevention and treatment of EA. Its mechanism of action involves the inhibition of pain signals mediated by traditional μ-receptor activation and potential new mechanism based on neural-endocrine-immune network， including regulation of microglial inflammatory pathways， and the modulation of cytokines and chemokines，etc. Clinical studies have shown that remifentanil can significantly shorten the recovery time， reduce the incidence of EA， and further optimize the analgesic effect and recovery quality by combining with other drugs （such as local anesthetics， sedatives， and opioid drugs）. Future research should further explore the mechanism of action of remifentanil， optimize clinical treatment strategies， and conduct large- scale clinical trials to standardize the drug use plan， while paying attention to its long-term effects and the development of multimodal treatment plans to promote the further development of EA prevention and treatment plans.

ObjectiveTo investigate the influencing factors for the clinical outcome of patients with drug-induced liver injury （DILI）， and to establish a nomogram prediction model for validation. MethodsA retrospective analysis was performed for the general information and laboratory data of 188 patients with DILI who were admitted to Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology from January 2017 to December 2022， and according to their clinical outcome， they were divided into good outcome group with 146 patients and poor outcome group with 42 patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Logistic regression analyses were used to investigate the independent influencing factors for the clinical outcome of DILI patients. R Studio 4.1.2 software was used to establish a nomogram model， and calibration curve， receiver operating characteristic （ROC） curve， and decision curve analysis （DCA） were used to perform internal validation. ResultsThe univariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI， platelet count， cholinesterase， albumin， prothrombin time activity， IgM， and IgG were associated with adverse outcomes in patients with DILI. The multivariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI （odds ratio ［OR］=0.072， 95% confidence interval ［CI］： 0.022‍ ‍—‍ ‍0.213， P<0.001）， clinical classification （OR=0.463， 95%CI： 0.213‍ ‍—‍ ‍0.926， P=0.039）， alanine aminotransferase （OR=0.999， 95%CI： 0.998‍ ‍—‍ ‍1.000， P=0.025）， prothrombin time activity （OR=0.973， 95%CI： 0.952‍ ‍—‍ ‍0.993， P=0.011）， and IgM （OR=1.456， 95%CI： 1.082‍ ‍—‍ ‍2.021， P=0.015） were independent influencing factors for clinical outcome in patients with DILI. The nomogram prediction model was established， and after validation， the calibration curve was close to the reference curve. The area under the ROC curve was 0.829， and the DCA curve showed that the model had good net clinical benefit. ConclusionThe nomogram prediction model established in this study has good clinical calibration， discriminative ability， and application value in evaluating the clinical outcome of patients with DILI.

The liver plays an important regulatory role in maintaining the dynamic balance of coagulation and anticoagulation in the body. Such dynamic balance is fragile in patients with liver cirrhosis， and the risk of bleeding can be increased due to reductions in coagulation factors and platelet count and excessive fibrinolysis； meanwhile， thrombus can be formed due to the increases in von Willebrand factor and coagulation factor Ⅷ， the reductions in anticoagulant protein C and anticoagulant protein S， the increase in thrombin-generating potential， and alterations in antifibrinolytic components. This article reviews the mechanisms of coagulation disorder in liver cirrhosis， so as to help clinicians with the prevention and treatment of bleeding or thrombotic disorders in patients with liver cirrhosis.

Objective:To investigate the status quo of educational and teaching research in community bases for general practice standardized residency training in China.Methods:The studies related to education research in community bases for general practice standardized residency training were searched from Chinese Journal Full Text Database (CNKI), Wanfang Database and China Science and Technology Journal Database (VIP) from inception to November 30, 2023. The keywords of "standardized training of general practitioner residents" or "general practice standardized training" or "general practitioner standardized training" or "general practice training" and "community-based teaching " or "community training" "community base" or "community teaching" were used for search, and affiliations of authors should contain"community health service center". The literature was read and summarized using Endnote and Excel software.Results:A total of 171 articles were retrieved that met the criteria, and 130 articles were finally selected for analysis according to the quality review criteria of the literature. The authors of articles were distributed in 78 institutions of 17 provinces or regions, with 9 provinces or regions having a total of 123 articles (94.6%) with 2 published articles or more, of which the highest number was found in Beijing and Shanghai. Seventeen institutions published 2 or more articles with a total of 69 articles (53.1%), including 67 articles (51.5%) were co-authored by 2 units. The ranking top ten institutions in terms of the number of articles published were 5 community health service centers in Beijing, 4 in Shanghai (co-authored with Shanghai Zhongshan Hospital). There were 46 articles (35.4%) published in core journals and 55 articles (42.3%) with fund-supported projects. The studies presented teaching methods, teaching and training contents, teaching evaluation and effects, teacher training, teaching base construction and information technology application.Conclusion:The educational and teaching research in community bases for general practice standardized training in China has gradually received attention, the researches were mainly carried out by community medical institutions, but the overall quality of research needs to be further improved.

OBJECTIVE To develop a questionnaire of the Knowledge-Attitude-Practice （KAP） for patients receiving oral anticoagulant therapy. METHODS Under the guidance of the theory of KAP， literature analysis and interview method were used to design the initial KAP questionnaire for patients treated with oral anticoagulants. Delphi method was adopted to consult the initial questionnaire and modify the questionnaire based on expert suggestions to form the final questionnaire. RESULTS Two rounds of consultation were conducted with 18 experts， and 18 questionnaires were sent out and recovered in each round， so the positive coefficient of experts was 100%. The expert authority coefficient was 0.94. The average importance scores for all dimensions， factors， and items of the questionnaire in both rounds were ≥4 points. The coefficient of variation was ≤0.25. The Kendall’s concordance coefficient for the overall questionnaire and the three dimensions of knowledge， attitude， and practice ranged from 0.09 to 0.34 （all P＜0.05）. Following the first round of expert consultation， four items were modified， two items were deleted， and five items were added； after the second round of expert consultation， ten items were modified. The final version of the questionnaire included three dimensions （knowledge， attitudes， and practice）， 17 questionnaire factors， and 40 items. CONCLUSIONS The questionnaire has high reliability and scientific validity with relatively concentrated expert opinions. It is suitable for assessing the knowledge， attitudes， and practice status of patients receiving oral anticoagulant therapy.

Objective: To explore the network structure characteristics and core items of rural middle school students suffering from campus bullying and anxiety symptoms, so as to provide a reference basis for the precise prevention and intervention of the comorbidity of campus bullying and anxiety symptoms. Methods: From September 2021 to March 2022, a multi stage random cluster sampling method was used to select 1 920 rural middle school students from Xuzhou. The Chinese version of the Olweus Bully/Victim Questionnaire was used to investigate the situation of campus bullying, and the Chinese version of the Generalized Anxiety Disorder (GAD-7) was used to assess anxiety symptoms. The network analysis method was used to construct the network between suffering from campus bullying and anxiety symptoms of rural middle school students to evaluate the centrality, bridge strength, stability and accuracy of each item. Results: The total score of suffering from campus bullying symptoms of rural middle school students was (10.42±3.26) points, and the total score of anxiety symptoms was (11.47±4.93) points. The symptom with the highest strength and expected influence was "unable to stop or control one s worry emotions", and the node strength and expected influence value was 1.041 7. The nodes "feel nervous, anxious or irritable" and "unable to stop or control one s worry emotions" were most closely related. The symptoms with the highest bridge strength were "others give me ugly nicknames to scold me or make fun of and satirize me" and "unable to stop or control one s worry emotions". Conclusions Rural middle school students suffering from campus bullying is related to anxiety symptoms. Accurate intervention according to the intervention targets may minimize the negative impact of suffering from campus bullying and anxiety symptoms on rural middle school students.

Objective To investigate the clinical effect of apical microsurgery combined with guided bone regeneration(GBR)on refractory apical periodontitis and masticatory function.Methods A total of 82 patients with refractory apical periodontitis admitted to our hospital from June 2019 to September 2021 were selected as the study subjects,and they were divided into the control group and the com-bined group according to the random number table,with 41 cases in each group.The control group was treated with apical microsurgery,and the combined group was treated with apical microsurgery combined with GBR.The clinical efficacy,masticatory function and the levels of bone absorption markers[Wnt3a,osteoprotegerin(OPG),receptor activator of nuclear factor-κB ligand(RANKL)]of patients in the two groups were compared.Results The total effective rate of the combined group(100%)was higher than that of the control group(85.37%),the difference was statistically significant(P<0.05).The masticatory efficiency and bite force of patients in both groups increased gradually 3,6 and 12 months after operation(P<0.05),which were higher in the combined group compared with the control group(P<0.05).The tooth mobility of patients in both groups decreased gradually 3,6 and 12 months after operation,and the tooth mobility of patients 3 and 6 months after operation in the combined group were lower than those in the control group(P<0.05).The levels of Wnt3a and OPG of patients 1 week after operation in both groups increased,which were higher in the combined group compared with the control group(P<0.05).The RANKL level of gingival crevicular fluid of patients 1 week after operation in both groups decreased,and which was lower in the combined group compared with the control group(P<0.05).Conclusion The microapical surgery combined with GBR is effective for refractory apical periodontitis,which can effectively inhibit bone resorption,and improve masticatory function.

At present,precise radiotherapy has been widely used through the development with many years,but the existing technique still is limited by the limitation of tolerance dose of normal tissues,which cannot achieve the optimal goal of treating tumor.Flash radiotherapy(Flash-RT)is one kind of radiotherapy technique that uses the beam with ultra-high dose rate(UHDR)to conduct irradiation,which can furthest treat tumors while significantly reduce radiation injury of normal tissues.But until now,the biological mechanism,key physical parameters and triggering mechanism of Flash-RT are still unclear,and its principle and clinical translational application are still in the stage of research.This review clarified the technological advance and clinical translational application of Flash-RT research through summarized the relevant research of Flash-RT.