BACKGROUND:Psoralen has a strong anti-osteoporotic activity and may have a restorative effect on chemotherapy-induced osteoporosis. OBJECTIVE:To explore the restorative effect of psoralen on the osteogenic differentiation of bone marrow mesenchymal stem cells in mice inhibited by cyclophosphamide and its mechanism. METHODS:C57BL/6 mouse bone marrow mesenchymal stem cells were isolated and cultured.Effect of psoralen on viability of bone marrow mesenchymal stem cells was detected by MTT assay.Osteogenic induction combined with alkaline phosphatase staining was used to determine the optimal dose of psoralen to restore the osteogenic differentiation of bone marrow mesenchymal stem cells inhibited by cyclophosphamide.The mRNA expression levels of Runx2,alkaline phosphatase,Osteocalcin,osteoprotegerin,and Wnt/β-catenin signaling pathway-related genes Wnt1,Wnt4,Wnt10b,β-catenin,and c-MYC were measured by RT-qPCR at different time points under the intervention with psoralen.The protein expression of osteogenic specific transcription factor Runx2 and Wnt/β-catenin signaling pathway related genes Active β-catenin,DKK1,c-MYC,and Cyclin D1 was determined by western blot assay at different time points under the intervention with psoralen. RESULTS AND CONCLUSION:(1)There was no significant effect of different concentrations of psoralen on the viability of bone marrow mesenchymal stem cells.The best recovery of the inhibition of osteogenic differentiation of bone marrow mesenchymal stem cells caused by cyclophosphamide was under the intervention of psoralen at a concentration of 200 μmol/L.(2)Psoralen reversed the reduction in osteogenic differentiation marker genes Runx2,alkaline phosphatase,Osteocalcin and osteoprotegerin mRNA expression and Runx2 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(3)Psoralen reversed the decrease in Wnt/β-catenin pathway-related genes Wnt4,β-catenin,c-MYC mRNA and Active β-catenin,c-MYC,and Cyclin D1 protein expression and the increase in DKK1 protein expression in bone marrow mesenchymal stem cells caused by cyclophosphamide conditioned medium.(4)The results showed that cyclophosphamide inhibited osteogenic differentiation of bone marrow mesenchymal stem cells in mice,and psoralen had a restorative effect on it.The best intervention effect was achieved at a concentration of 200 μmol/L psoralen,and this protective effect might be related to the activation of Wnt4/β-catenin signaling pathway by psoralen.

BackgroundMigraine is a common chronic neurological disease， and patent foramen ovale （PFO） has been closely associated with migraine. Current research primarily focuses on the pathological mechanism and the therapeutic effects of interventional closure， with limited attention paid to the impact of PFO on sleep quality in migraine patients. ObjectiveTo compare the difference in sleep quality between PFO-positive and PFO-negative migraine patients， and to analyzes influencing factors of sleep quality in PFO-positive migraine patients， so as to provide references for clinical interventions to improve sleep quality in PFO-positive migraine patients. MethodsA total of 673 migraine patients who met the diagnostic criteria of migraine in the International Classification of Headache Disorders， third edition （ICHD-3）， and all patients underwent contrast-enhanced transcranial Doppler （c-TCD） and transthoracic echocardiographic right heart contrast echocardiography （cTTE） in the Third Hospital of Mianyang from January 2020 to October 2024. Basic demographic data were collected using a self-designed questionnaire， headache severity was assessed with the Visual Analogue Scale （VAS）， and sleep quality was invaluated using the Pittsburgh Sleep Quality Index （PSQI）. PFO patients was diagnosed through c-TCD combined with c-TTE. Binary logistic regression analysis was employed to examine the influencing factors of sleep quality in PFO-positive migraine patients. ResultsA total of 673 （100.00%） migraine patients were enrolled， including 223 PFO-positive cases （33.14%） and 450 PFO-negative cases（66.86%）. The PFO-positive group showed significantly more severe headache severity （χ²=15.799， P<0.01） and poorer sleep quality （χ²=14.377， P<0.01） compared with PFO-negative group. PFO-positive patients demonstrated significantly higher barrier factor scores of sleep quality， sleep latency， sleep efficiency， sleep disturbance， hypnotic medication use， and daytime dysfunction compared with PFO-negative counterparts （t=3.634， 3.269， 2.785， 3.428， 2.907， 3.637， Bonferroni adjust P<0.05/7=0.007）.By contrast， no significant difference was noted in sleep duration scores between the two groups（t=2.349， Bonferroni adjust P>0.05/7=0.007）.The Binary Logistic regression analysis revealed that age （OR=1.021， 95% CI： 1.001~1.041）， headache severity （OR=6.030， 95% CI： 4.085~8.901）， and PFO grade （OR=1.893，95% CI： 1.288~2.784）were significant influencing factors for sleep quality in migraine patients with PFO. ConclusionMigraine patients with PFO-positive exhibited poorer sleep quality compared wtih PFO-negative patients. Older age， higher headache servity， and more severe PFO grade are identified as risk factors for impaired sleep quality in PFO-positive migraine patients.

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

Objective Summarizes the current research status of defensive medicine in China and provides references for future research.Methods The search period spans from the inception of the database to March 2024.CNKI,Wan-fang Data,Web of Science,PubMed databases were queried,followed by literature screening based on predeter-mined inclusion and exclusion criteria.The current landscape of defensive medicine research in China was synthe-sized and categorized based on fundamental research characteristics,measurement methodologies,influencing fac-tors,and other relevant aspects.Results A total of 24 Chinese literature sources and 4 foreign literature sources were incorporated,indicating a prevalent occurrence of defensive medicine in China.Measurement tools for defen-sive medicine exhibit variability across different studies.Key influencing factors encompass doctor's demographic vari-ables such as gender,age,and professional status,institutional factors like legal frameworks and medical in-surance,and sociol-cultural factors such as doctor-patient relationships and adverse public perceptions.Conclusion Defensive medicine is relatively widespread and influenced by various factors in China.It's urgent to explore the for-mation mechanism of defensive medicine from multiple perspectives and provide evidence for passive defen-sive medicine governance.

Objective To clarify the influencing factors of defensive medicine and provide ideas for preventing and re-solving defensive medicine.Methods Literature related to defensive medicine was searched,personnel related to de-fensive medicine were interviewed,and literature and interview data were coded with the method of grounded theo-ry,and related concepts and categories were summarized.Results After three levels of coding,52 initial concepts,23 initial categories,7 sub-categories and 3 main categories were sorted out,and the correlation among influencing factors was analyzed to build a three-dimensional model of"doctor-patient relationship-institutional system-social environment"influencing factors and their mechanism of action.Conclusion The influencing factors of defensive medi-cine mainly include doctor-patient relationship,institutional system and social environment.The three factors have an impact on defensive medicine through different mechanisms of action,which provides qualitative evidence for comprehensive analysis of factors in related studies of defensive medicine.

Objective By exploring the conditional configuration effect of negative defensive medicine behavior,the formation mechanism and causal path of negative defensive medicine are explained,and systematic suggestions are provided for negative defensive medicine behavior,so as to improve the rational utilization of health resources.Methods NCA and fsQCA are used to conduct configuration analysis on factors influencing passive defensive medical behavior,output the conditional configuration,and further analyze the configuration effects among the influencing factors.Results The antecedent conditions of negative defensive medicine include systemic mechanisms,institutional norms,social culture,doctor-patient relationships,and self-efficacy.Ultimately,two paths contributing to passive defensive medical behavior emerge:environment conduction type and efficiency-environment joint conduction type,their consistency is 0.830.Conclusion To reduce the negative defensive medical behavior,it should pay atten-tion to improving the institutional environment and improving doctors'self-efficacy,establish a fair and reasonable external institutional environment,create an honest and harmonious cultural atmosphere,strengthen the training of doctors'professional ability and improve the doctor-patient relationship,so as to improve the rational use of health resources.

Objective To understand the status of behavioral intentions of defensive medical treatment in medical students,and explore the relationship between practice environment and behavioral intentions of defensive medical treatment.To provide reference for reducing the tendency of defensive medicine(DM)behavior of medical students and improving the negative effects of DM.Methods A web-based questionnaire survey was conducted among medi-cal students in four medical colleges in Heilongjiang Province.The structural equation modeling of the relationship be-tween practice environment and behavioral intentions of defensive medical treatment in medical students was con-structed by Amos 26.0 software.Results The mean score of medical students'behavioral intentions of positive and negarive defensive medical treatment was 44.49-6.90 and 20.06-6.83,respectively.The behavioral intention of posi-tively defensive medical treatment was positively associated(β=0.892,P＜0.05)with cognition of doctor-patient relationship.While the behavioral intention of negative defensive medical treatment was positively correlated(β=0.403,0.343,P＜0.05)with environment cognition,perception of risk and negatively correlated(β=-0.726,P＜0.05)with cognition of doctor-patient relationship.As an intermediary variable,the direct and indirect effects of cog-nition of doctor-patient relationship on negative defensive medical behavior tendency were-0.470 and 0.043,the difference was statistically significant(P＜0.05).Conclusion Improving cognition of medical students'doctor-pa-tient relationship is beneficial to understand defensive medical treatment for medical students.The negative defen-sive medical behavior tendency of medical students should be reduced by reducing their negative cognition of environ-ment or improving their cognition of doctor-patient relationship.

Objective To evaluate the applicability of a modified U-shaped forearm flap for the repair of small-and medium-sized defects in the oral and maxillary areas to provide a reference for clinicians.Methods This study was re-viewed and approved by the Ethics Committee,and informed consent was obtained from the patients.Ten patients with small-and medium-sized defects in the oral and maxillary areas underwent surgical repair using modified U-shaped fore-arm flaps.There were 8 males and 2 females aged 43-72 years.The donor site was apposed primarily after harvesting the modified U-shaped forearm skin flap.The flaps ranged from 6 cm × 4 cm to 8 cm × 5 cm in size.Six months after the operation,hand movements(finger extension,fist clenching,wrist rotation upward and wrist rotation downward),the forearm donor site,hand sensations and the satisfaction score for the postoperative quality of the scar at the donor site were evaluated(0 to 10;0:very unattractive,10:very satisfactory).Results A total of 10 patients with modified U-shaped forearm flaps survived.One patient developed venous crisis 24 hours after surgery and survived after surgical ex-ploration.Delayed healing occurred at the donor site of the forearm in 1 patient,and the wounds at the donor site of the forearm in the other patients all healed in the first stage.One patient presented with dysesthesia in the hand 2 weeks af-ter surgery and recovered within 3 months.Six months after surgery,all patients had no limited hand movement and no paresthesia at the forearm donor site or hand.The patients were basically satisfied with the appearance of the donor site,and the average satisfaction score of the subjective questionnaire was 8.4 points.Conclusion Modified U-shaped fore-arm flaps can directly close forearm donor site wounds,which avoids surgical trauma to the secondary donor site and sig-nificantly reduces related complications.Modified U-shaped forearm flaps provide an alternative to conventional forearm flaps for the repair of small-and medium-sized defects in the oral and maxillary areas.

Objective:To evaluate direct and indirect costs for schizophrenia,major depressive disorder(MDD)and bipolar disorder,and to compare their differences of cost composition,and to explore the drivers of the total costs.Methods:A total of 3 175 inpatients with schizophrenia,MDD,and bipolar disorder were recruited.In-patient's self-report total direct of medical costs outpatient and inpatient,out-of-pocket costs,and direct non-medical costs were regarded as direct costs.Productivity loss and other loss caused by damaging properties were defined as indirect costs.The perspectives of this study included individual and societal levels.Multivariate regression analysis was applied for detecting the factors influencing disease costs.Results:The total cost of schizophrenia was higher than those of MDD and bipolar disorder at individual and societal levels.The indirect costs of three mental disorders were higher than the direct costs,and the indirect cost ratio of bipolar disorder was higher than those of schizophre-nia and MDD.Age,gender,working condition and marital status(P＜0.05)were the important drivers of total costs.Conclusion:The economic burden of the three mental disorders is relatively heavy.Schizophrenia has heaviest disease burden,and the productivity loss due to mental disorders is the driving force of the soaring disease cost

"Balance between yin and yang,the spirit is treated"means the best health state of the human body.The theory of yin and yang is the foundation of TCM theory,and the key to the treatment of chronic skin diseases is to regulate yin and yang.The key to the balance of yin and yang lies in the sufficiency of yang-qi.Sufficient yang-qi can guarantee the defense outside is solid and dense.The healthy-qi inside can avoid the invasion of pathogenesis.The invisible pathogenesis is difficult to transform into tangible pathogenesis.In the clinical syndromes,it has been found that the lack of yang-qi is one of the important reasons for the occurrence and development of skin diseases.By warming yang and dispersing pathogenic factors,dissolving muscles and dispelling wind,reconciling nutrient and defense,warming and dissipating cold,clearing heat and detoxifying,nourishing blood and moistening dryness,etc.,the deficiency yang can be warmed,the yang can be concealed,the balance between yin and yang can be achieved,and the diseases can be eliminated.