Aim To explore the mechanism of ligustil-ide(LIG)improving demyelination by inhibiting in-flammatory response in mice with distal middle cerebral artery occlusion(dMCAO)through AIM2/caspase-1 signal pathway.Methods Thirty C57BL/6N male mice were randomly divided into three groups:sham operation group(Sham group,n=10),model group(dMCAO group,n=10)and treatment group(LIG group,n=10).The dMCAO mouse model was estab-lished by electrocoagulation in dMCAO group and LIG group.The mice were scored by Longa after waking up,and the changes of cerebral blood flow were moni-tored by laser speckle blood flow imaging system after dMCAO.One hour after modeling,LIG(30 mg·kg-1·d-1)was injected intraperitoneally in LIG group,and the same amount of normal saline was injected in sham group and dMCAO group for one week until the end of the experiment.The mice in each group were stained with TTC,and the brain injury was observed pathologically.Fatigue turning bar test and open field test were used to evaluate the motor function and anxie-ty degree of mice,and then the brain tissues of mice were taken for black gold staining to compare the chan-ges of myelin sheath in each group.Immunofluores-cence staining was used to detect the average fluores-cence intensity of MBP,IBA1 and GFAP in CC,CPU and CX regions of mouse brains.ELISAwas used to de-tect the contents of TNF-α,IL-6,IL-1 β,IL-17A and BDNF in brain tissue proteins of mice.Western blot-ting was used to detect the protein expressions of AIM2,caspase-1 and ASC-in each group.Results Compared with the dMCAO group,the infarct area was reduced,the behavior was significantly improved and the demyelination was reduced in the LIG group.The expression of MBP protein in CC,CPU and CX regions increased(P＜0.05),the expression of IBA1 in CX decreased(P＜0.01),and the expression of GFAP in-creased in CC,CPU and CX regions(P＜0.01).The results of ELISA showed that the levels ofTNF-α(P＜0.01),IL-6(P＜0.01),IL-1β(P＜0.05)and IL-17A(P＜0.01)significantly decreased,while the ex-pression of BDNF increased(P＜0.05).The protein expression levels of AIM2,caspase-1 and ASC in mouse brain decreased after treatment(P＜0.01).Conclusion LIG has a protective effect on demyelina-tion in dMCAO mice,which may be related to the inhi-bition of AIM2/caspase-1 signaling pathway and in-flammation and to the promotion of BDNF secretion.

Objective:To integrate and analyze the trend of the disease burden of tracheal,bronchus,and lung cancer(TBL)attributable to secondhand smoke in China from 1990 to 2021 and to analyze future projections,aiming to provide data support for the prevention and treatment of TBL in China.Methods:Based on the global burden of disease(GBD)2021 database,TBL with ICD-10 disease classification C33,C34-C34.92 was studied.Using secondhand smoke as a risk factor,the data on TBL mortality and disability-adjusted life year(DALY)due to secondhand smoke in China from 1990 to 2021 were further age-standardized.Using Joinpoint 4.7.1 regression analysis model to calculate annual percentage change(APC)and average annual percentage change(AAPC),Hiplot software was used to plot disease burden data for different ages and genders,and R 4.3.1 software was used to construct a grey model GM(1,1)to predict the predicted value and trend of TBL disease burden attributed to secondhand smoke in China from 2022 to 2031.Results:From 1990 to 2021,the TBL mortality rate,age-standardized mortality rate,and DALY rate attributed to secondhand smoke in China increased from 1.76/100 000,2.63/100 000,and 49.43/100 000 to 4.08/100 000,2.80/100 000,and 95.57/100 000,respectively;the growth was 131.18%,6.45%,and 93.34%;the age-standardized DALY rate decreased from 65.04/100 000 to 63.32/100 000 with the reduction of 2.65%.The results of the Joinpoint regres-sion showed that the AAPC(95%CI)of mortality,age-standardized mortality rate,and DALY rate for TBL were 2.75(2.58-2.93)%,0.16(0.11-0.21)%,and 2.15(2.11-2.18)%,respectively,with an overall increasing trend;the AAPC(95%CI)of age-standardized DALY rate was-0.14(-0.40-0.12)%,with an overall fluctuating and unchanged trend and it was higher in males than in females.In both 1990 and 2021,the TBL mortality rate attributable to secondhand smoke in China gradually increased with age,and the DALY rate first increased and then slowed down with age.The main groups of the burden of disease were the elderly and males.The grey prediction model GM(1,1)showed that the age-standardized mortality rate of TBL attributable to secondhand smoke from 2022 to 2031 showed a slow increasing trend,and the predicted value in 2031 would increase to 2.95/100 000.The age-standardized DALY showed a slow decreasing trend,and the predicted value in 2031 would decrease to 63.83/100 000.Conclusions:From 1990 to 2021,the TBL mortality,age-standardized mortality,and DALY rates attributable to secondhand smoke in China increased,and the age-standardized DALY rate decreased.Men and the elderly are the main groups affected by TBL.Appropriate measures should be formulated to reduce exposure to and contact with secondhand smoke,tak-ing into account gender and age differences.Additionally,efforts should be made to strengthen secondhand smoke prevention and public health education.

Objective:To analyze the learning curve of TiRobot-assisted lumbar pedicle screw fixation (LPSF) by cumulative sum (CUSUM) test method.Methods:The clinical data of 50 patients who underwent TiRobot-assisted LPSF from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. CUSUM analysis and learning curve fitting were performed with robot usage time as the main indicator with the time for each step refined (robot registration time, path planning time and guide wire placement time), to select the best learning curve fitting model with the R2 value closest to 1. Using the turning point of the learning curve as the boundary, the learning curve was divided into two stages as learning stage and maturity stage, and then the observation indexes were compared between the two stages. Results:All 50 patients successfully completed the surgery without perioperative complications, with a total of 244 pedicle screws implanted. The total robot usage time and robot registration time showed a gradually decreasing trend with the increase of case number, and the learning curves were successfully fitted and reached their peaks at the seventeenth and thirteenth cases respectively. The entire learning process was divided into learning stage (17 cases) and maturity stage (33 cases) based on the turning point of the learning curve of total robot usage time. The path planning time and guide wire placement time did not show significant changes with the increase in the case number. The total robot usage time, robot registration time and the intraoperative blood loss in the learning stage were significantly higher than those in the maturity stage: (35.35 ± 1.58) min vs. (30.61 ± 0.43) min, (20.83 ± 1.56) min vs. (14.94 ± 0.29) min and 400 (150, 500) ml vs. 200 (110, 300) ml, the guide wire placement time of per screw was significantly lower than that in the maturity stage: 2.00 (1.83, 2.34) min/screw vs. 2.33 (2.13, 2.69) min/screw, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the path planning time, path planning time of per screw, guide wire placement time and the accuracy of screw placement between two stages ( P>0.05). Conclusions:TiRobot-assisted LPSF is a new technology with safety and effectiveness, and it has a relatively short learning curve. To achieve technological maturity, at least 17 surgeries are required with accumulated experience, and the robot registration is the main step of the learning process. After reaching maturity stage, the robot usage time is significantly shortened and intraoperative trauma is significantly reduced while the relatively high screw placement accuracy is ensured.

Aim To explore the mechanism of Lycium barbarum glycopeptide(LbGP)improving aging in rat primary ovarian granulosa cells.Methods This study divided the cells into a normal group,a DOX group,and four different LbGP concentration treatment groups post-DOX intervention.Results Cell proliferation was assessed using CCK-8,EDU,and Ki67 assays,while aging markers and mitochondrial function-related fac-tors were detected using immunofluorescence and West-ern blotting.The results showed that,compared to the DOX group,LbGP treatment significantly increased cell viability(P＜0.05)and promoted proliferation(P＜0.05).Post LbGP treatment,the β-galactosidase-posi-tive area in cells was significantly reduced compared to the DOX group(P＜0.05).Immunofluorescence re-sults indicated that,compared to the DOX group,levels of p21 and γH2AX significantly decreased(P＜0.05),while pRB increased(P＜0.05)after LbGP treatment.Western blot results showed that,compared to the DOX group,the aging phenotype proteins p21 and p53 significantly decreased(P＜0.05),and pRB notably increased(P＜0.05)in the LbGP treatment group.The release of cytC into the cytoplasm and the activated caspase-9 significantly decreased(P＜0.05);levels of CAMKK2,pAMPK,and mitochondrial calcium homeostasis regulator MCU increased(P＜0.05);nuclear energy metabolism-related proteins SirT1,PGC1α/β and ATP5A1 significantly increased(P＜0.05);compared to the DOX group,ROS levels significantly decreased after LbGP treatment(P＜0.05).Conclusions The results suggest that LbGP can ameliorate DOX-induced aging in rat primary ovar-ian granulosa cells,potentially through the upregulation of the CAMKKβ/AMPK signaling pathway,thereby im-proving mitochondrial calcium homeostasis and increas-ing the expression levels of cell energy metabolism-re-lated regulatory proteins.This provides an experimen-tal basis for LbGP's potential role in supporting the im-provement of ovarian function.

Aim To explore the mechanism of ligustil-ide(LIG)improving demyelination by inhibiting in-flammatory response in mice with distal middle cerebral artery occlusion(dMCAO)through AIM2/caspase-1 signal pathway.Methods Thirty C57BL/6N male mice were randomly divided into three groups:sham operation group(Sham group,n=10),model group(dMCAO group,n=10)and treatment group(LIG group,n=10).The dMCAO mouse model was estab-lished by electrocoagulation in dMCAO group and LIG group.The mice were scored by Longa after waking up,and the changes of cerebral blood flow were moni-tored by laser speckle blood flow imaging system after dMCAO.One hour after modeling,LIG(30 mg·kg-1·d-1)was injected intraperitoneally in LIG group,and the same amount of normal saline was injected in sham group and dMCAO group for one week until the end of the experiment.The mice in each group were stained with TTC,and the brain injury was observed pathologically.Fatigue turning bar test and open field test were used to evaluate the motor function and anxie-ty degree of mice,and then the brain tissues of mice were taken for black gold staining to compare the chan-ges of myelin sheath in each group.Immunofluores-cence staining was used to detect the average fluores-cence intensity of MBP,IBA1 and GFAP in CC,CPU and CX regions of mouse brains.ELISAwas used to de-tect the contents of TNF-α,IL-6,IL-1 β,IL-17A and BDNF in brain tissue proteins of mice.Western blot-ting was used to detect the protein expressions of AIM2,caspase-1 and ASC-in each group.Results Compared with the dMCAO group,the infarct area was reduced,the behavior was significantly improved and the demyelination was reduced in the LIG group.The expression of MBP protein in CC,CPU and CX regions increased(P＜0.05),the expression of IBA1 in CX decreased(P＜0.01),and the expression of GFAP in-creased in CC,CPU and CX regions(P＜0.01).The results of ELISA showed that the levels ofTNF-α(P＜0.01),IL-6(P＜0.01),IL-1β(P＜0.05)and IL-17A(P＜0.01)significantly decreased,while the ex-pression of BDNF increased(P＜0.05).The protein expression levels of AIM2,caspase-1 and ASC in mouse brain decreased after treatment(P＜0.01).Conclusion LIG has a protective effect on demyelina-tion in dMCAO mice,which may be related to the inhi-bition of AIM2/caspase-1 signaling pathway and in-flammation and to the promotion of BDNF secretion.

Objective:The predictive value of oxidized low density lipoprotein(ox-LDL)and electrocardiogram(ECG)ischaemia grade for major adverse cardiovascular events(MACE)in patients with ST elevation myocardial infarction(STEMI)after percutaneous coronary intervention(PCI)was assessed by a retrospective cohort study de-sign.Methods:A total of 336 STEMI patients admitted to Cangzhou People's Hospital between October 2019 and May 2022 were selected,and the medical record information was obtained through the hospital medical record sys-tem,and all patients received PCI and physician-recommended basic treatment.With occurrence of MACE with in 12-month follow-up as the evaluation index,they were divided into MACE group(n=65)and no MACE group(n=271).Multifactorial Logistic regression model was used to study the influencing factors of MACE after PCI in STEMI patients,and Spearman test for association of ox-LDL level,ECG ischaemia grade with MACE after PCI.ROC curve was used to evaluate the predictive efficacy of ox-LDL,ECG ischaemia grade and their combination for MACE after PCI.Results:The overall MACE incidence was 19.35％.Compared with patients in no MACE group,those in MACE group had significant higher ox-LDL level[46.34(29.46,66.29)U/L vs.33.00(23.02,50.03)U/L]and proportion of ECG grade Ⅲ ischaemia(64.62％vs.42.80％)(P＜0.01 all).Multifactorial Logistic re-gression analysis showed that ox-LDL(OR=1.022,95％CI 1.011～1.033,P=0.001)and ECG grade Ⅲ ischae-mia(OR=1.878,95％CI 1.007～3.504,P=0.048)were the independent risk factors of post-PCI MACE in STEMI patients.Spearman test showed that ox-LDL and ECG grade Ⅲ ischaemia were positively correlated with post-PCI MACE(r=0.209,0.173,P＜0.001 all).ROC curve analysis showed that the AUCs of ox-LDL,ECG grade Ⅲ ischaemia and their combination in predicting post-PCI MACE were respectively 0.653(95％CI 0.599～0.704),0.609(95％CI 0.555～0.662)and 0.758(95％CI 0.709～0.803),in which the predictive value of the combination of the two was significantly higher than any single detection(Z=2.030,3.097,P=0.042,0.002).Conclusion:ox-LDL combined with ECG ischaemia grading has a high predictive value for the occurrence of MACE with in 12 months after PCI in STEMI patients.

Myocardial fibrosis(MF)is the leading cause of car-diac insufficiency.Its complex pathogenesis and lack of effective treatment are key issues to be addressed in the cardiovascular field.Mitochondrial quality control system(MQC)is an impor-tant mechanism for eukaryotic cells to maintain the stability of mitochondrial form,quantity and quality.MQC disorders,which are characterized by low level of mitochondrial biogenesis,exces-sive mitochondrial oxidative stress,mitochondrial autophagy de-fect and mitochondrial dynamics disorder,play a crucial role in mediating the pathophysiological process of MF.Consequently,this article reviews the role of MQC in MF pathogenesis and the latest research,in order to better understand the molecular mech-anism of MF and provide reference for the development of more natural drugs in the future.

Objective:To analyze the learning curve of TiRobot-assisted lumbar pedicle screw fixation (LPSF) by cumulative sum (CUSUM) test method.Methods:The clinical data of 50 patients who underwent TiRobot-assisted LPSF from January 2020 to December 2022 in Beijing Friendship Hospital, Capital Medical University were retrospectively analyzed. CUSUM analysis and learning curve fitting were performed with robot usage time as the main indicator with the time for each step refined (robot registration time, path planning time and guide wire placement time), to select the best learning curve fitting model with the R2 value closest to 1. Using the turning point of the learning curve as the boundary, the learning curve was divided into two stages as learning stage and maturity stage, and then the observation indexes were compared between the two stages. Results:All 50 patients successfully completed the surgery without perioperative complications, with a total of 244 pedicle screws implanted. The total robot usage time and robot registration time showed a gradually decreasing trend with the increase of case number, and the learning curves were successfully fitted and reached their peaks at the seventeenth and thirteenth cases respectively. The entire learning process was divided into learning stage (17 cases) and maturity stage (33 cases) based on the turning point of the learning curve of total robot usage time. The path planning time and guide wire placement time did not show significant changes with the increase in the case number. The total robot usage time, robot registration time and the intraoperative blood loss in the learning stage were significantly higher than those in the maturity stage: (35.35 ± 1.58) min vs. (30.61 ± 0.43) min, (20.83 ± 1.56) min vs. (14.94 ± 0.29) min and 400 (150, 500) ml vs. 200 (110, 300) ml, the guide wire placement time of per screw was significantly lower than that in the maturity stage: 2.00 (1.83, 2.34) min/screw vs. 2.33 (2.13, 2.69) min/screw, and there were statistical differences ( P<0.05 or <0.01). There were no statistical difference in the path planning time, path planning time of per screw, guide wire placement time and the accuracy of screw placement between two stages ( P>0.05). Conclusions:TiRobot-assisted LPSF is a new technology with safety and effectiveness, and it has a relatively short learning curve. To achieve technological maturity, at least 17 surgeries are required with accumulated experience, and the robot registration is the main step of the learning process. After reaching maturity stage, the robot usage time is significantly shortened and intraoperative trauma is significantly reduced while the relatively high screw placement accuracy is ensured.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics.Similarities and variations of components present significant analytical challenges.A two-dimensional(2D)liquid chromatography-mass spectrometry(LC-MS)method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium(CMS).A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated.For efficient and high-accuracy screening of CMS,a targeted method based on a self-constructed high resolution(HR)mass spectrum database of CMS components was established.The database was built based on the commercial MassHunter Personal Compound Database and Library(PCDL)software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening.On this basis,the unknown peaks in the CMS chromatograms were deduced and assigned.The molecular formula,group composition,and origins of a total of 99 compounds,of which the combined area percentage accounted for more than 95％of CMS components,were deduced by this 2D-LC-MS method combined with the MassHunter PCDL.This profiling method was highly efficient and could distinguish hundreds of components within 3 h,providing reliable results for quality control of this kind of complex drugs.