1.Asia-Pacific consensus statement on medication-related osteonecrosis of the jaw in patients with osteoporosis
Akira TAGUCHI ; Daisuke INOUE ; Jin-Woo KIM ; Keskanya KESKANYA ; Wai Sin CHAN ; Hee Dong CHAE ; Chung-Hwan CHEN ; Ching-Lung CHEUNG ; Eddie Siu Lun CHOW ; Yoon-Sok CHUNG ; Linsey GANI ; Muhammad Kamil BIN HASSAN ; Unnop JAISAMRARN ; Chakorn VORAKULPIPAT ; Nutchada SRIYARANYA ; Aasis UNNANUNTANA ; Tanawat AMPHANSAP ; Seng Bin ANG ; Fen Lee HEW ; Julie LI-YU ; Terence Ong Ing WEI ; Jeyakantha JEYAKANTHA ; Mark Anthony SANDOVAL ; Thawee SONGPATANASILP ; Monica Therese CATING-CABRAL ; Thanut VALLEENUKUL ; Lalita WATTANACHANYA ; Chih-Hsing CHIH-HSING ; Weibo XIA ; Jawl-Shan HWANG ; Hiroshi HAGINO ; Natthinee CHARATCHAROENWITTHAYA
Osteoporosis and Sarcopenia 2026;12(1):1-17
A unified consensus statement on medication-related osteonecrosis of the jaw (MRONJ) has not yet been established among the Asian member countries or regions of the Asian Federation of Osteoporosis Societies (AFOS). This study aimed to develop a consensus on MRONJ in patients with osteoporosis across these countries and regions. In this study, the term “Asia-Pacific” refers specifically to the Asian member countries and regions of AFOS. A structured survey consisting of nine MRONJ-related questions was distributed across 10 countries and regions to assess the level of agreement and summarize regional perspectives. In addition, a manual literature review and voting were conducted to evaluate the current evidence on MRONJ. The key aspects of MRONJ, including definition, staging, diagnosis, pathogenesis, risk factors, management, and prevention, were generally consistent among the AFOS countries and regions. The annual incidence and incidence rate of MRONJ associated with low-dose antiresorptive therapy in patients with osteoporosis ranged from 0.025% to 0.136% and 21 to 283 cases per 100,000 person-years, respectively. However, evidence regarding the benefits of drug discontinuation before dental surgery, such as tooth extraction, remains insufficient. Large-scale, multinational studies across AFOS countries and regions are warranted to determine the incidence of MRONJ better and evaluate the impact of antiresorptive drug discontinuation before dental procedures. These findings may contribute to the devel opment of effective evidence-based strategies for preventing MRONJ in patients with osteoporosis.
2.Prevalence and influencing factors of suspected sarcopenia among community-dwelling elderly patients with type 2 diabetes in Changning District, Shanghai
Xia LI ; Zhenping LU ; Dong CHEN ; Hua YANG ; Yu JIANG
Shanghai Journal of Preventive Medicine 2026;38(5):344-349
ObjectiveTo conduct sarcopenia-related screening and assessment among community-dwelling elderly patients with type 2 diabetes mellitus (T2DM) in Changning District of Shanghai, to analyze the current status and influencing factors of suspected sarcopenia in this population, and to provide references for the early prevention and treatment of sarcopenia. MethodsUsing a stratified random sampling method, elderly T2DM patients under management in the Chronic Disease Health Management System of Changning District in Shanghai were selected as the study subjects. Patients were screened for sarcopenia and underwent related health examinations according to the Chinese Expert Consensus on Diagnosis and Treatment of Sarcopenia in the Elderly (2021). Self-designed questionnaires were used to collect basic information, lifestyle habits and health status, and the Montreal Cognitive Assessment (MoCA) was employed to evaluate cognitive function. ResultsAmong 758 elderly patients with T2DM [average age: (72.19±6.19) years old], 214 patients were identified as having suspected sarcopenia,accounting for 28.23%. The proportion of suspected sarcopenia was higher in females (30.94%) than in males (24.08%) (χ²=4.20, P=0.040), and higher in older patients (χ²=22.26, P<0.001). Higher proportions of suspected sarcopenia were also observed among patients who followed a vegetarian diet (39.77%) (χ²=73.28, P=0.011), had diabetic foot (59.09%) (χ²=10.65, P=0.001), reported feeling fatigued most of the time (37.11%) (χ²=4.33, P=0.037), or had mild cognitive impairment (χ²=3.95, P=0.047). The duration of T2DM in the suspected sarcopenia group [(12.86±10.07) years old] was longer than that in the non-sarcopenia group [(9.73±8.63) years old] (t=3.79, P<0.001), and the average body mass index (BMI) in the suspected sarcopenia group [(22.17±2.45) kg⋅m-²)] was lower than that in the non-sarcopenia group [(25.11±3.26) kg⋅m-²)] (t=-11.41, P<0.001). Multivariate logistic regression analyses showed that older age (OR=1.08, 95%CI:1.047‒1.110) and longer duration of T2DM (OR=1.02, 95%CI:1.005‒1.043) were associated with a higher risk of suspected sarcopenia in elderly T2DM patients. Female elderly T2DM patients had a higher risk of suspected sarcopenia (OR=1.89, 95%CI:1.310‒2.733) than males, and those with diabetic foot (OR=3.66, 95%CI:1.341‒9.990) had a higher risk than those without diabetic foot. ConclusionThe proportion of elderly T2DM patients with suspected sarcopenia was relatively high. In community-based integrated health management, healthcare providers should pay more attention to elderly T2DM patients who are older, have longer disease duration, are female, or have diabetic foot, so as to identify risks early and implement targeted comprehensive interventions and health management.
3.The association between prefrontal cortex functional connectivity and clinical symptoms in patients with schizophrenia
Man DONG ; Yang TIAN ; Lifeng WANG ; Bingqian LIU ; Ranran XUE ; Xinxiu HE ; Xia LIU ; Shanling JI ; Hao YU
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(10):905-911
Objective:To investigate the functional characteristics of the prefrontal cortex in patients with schizophrenia (SCZ) during resting state and analyze its association with clinical symptoms.Methods:Twenty-eight hospitalized patients with SCZ (SCZ group) were selected from November 2023 to May 2024, and 28 healthy controls (HC group) were recruited concurrently. By using functional near-infrared spectroscopy (fNIRS) technology, data on the concentration changes of oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR) in the prefrontal cortex during resting state were collected from all subjects to measure cortical hemodynamic activity. Regional activation values and functional connectivity (FC) values among brain areas were analyzed. Clinical symptoms in patients were assessed using the positive and negative syndrome scale (PANSS).SPSS 25.0 software was employed for statistical analysis. Between-group comparisons were performed using independent samples t-tests or Mann-Whitney U tests. Spearman correlation analysis and general linear regression models were applied to examine relationships between prefrontal cortical functional characteristics and clinical symptoms. Results:The levels of HbO in the right inferior frontal gyrus and left frontal pole area were significantly higher in the SCZ group (1.5 (1.0, 3.0)μmol/L, 1.0 (1.0, 2.8)μmol/L) than those in the HC group (-0.01 (-0.05, 0.02)μmol/L, -0.02 (-0.07, 0.03)μmol/L) ( Z=-6.46, -6.50, both P<0.01). The levels of HbR in the bilateral dorsolateral prefrontal cortex were significantly higher in the SCZ group (0.02 (-0.01, 0.07)μmol/L, 0.01 (-0.01, 0.03)μmol/L) than those in the HC group (-0.01 (-0.03, 0.01)μmol/L, -0.01 (-0.02, 0.01)μmol/L) ( Z=-2.46, -1.98, both P<0.05).The SCZ group showed significantly higher HbO-based FC values in the frontal pole-temporal pole (0.49±0.21) and temporal pole-dorsolateral prefrontal cortex (0.36±0.25) compared to the HC group (0.33±0.18, 0.15±0.19) ( t=3.02, 3.44, both P<0.01). Conversely, the SCZ group exhibited significantly lower HbR-based FC in the frontal pole-inferior frontal gyrus (0.15±0.13) and inferior frontal gyrus-temporal pole (0.27±0.37) compared to the HC group (0.33±0.26, 0.77±0.48) ( t=-3.17, -4.23, both P<0.01). Correlation analysis revealed that in the SCZ group, the level of HbO in the right inferior frontal gyrus was positively correlated with negative symptoms, positive symptoms, excitement/hostility, and PANSS total score ( r=0.45-0.64, all P<0.05), and the level of HbO in the left frontal pole area was positively correlated with excitement/hostility and PANSS total score ( r=0.57, 0.50, both P<0.01), while the FC value between the frontal pole and temporal pole areas showed a negative correlation with excitement/hostility ( r=-0.39, P<0.05). Regression analysis demonstrated that, the HbO concentration in the right inferior frontal gyrus significantly positively predicted PANSS total score, positive symptoms, and negative symptoms ( β=0.70, 0.64, 0.55, all P<0.01).The HbO concentration in the left frontal pole area significantly positively predicted excitement/hostility ( β=0.77, P<0.01).The frontal pole-temporal pole HbO-based FC significantly negatively predicted excitement/hostility scores ( β=-0.42, P<0.01). Conclusion:Patients with SCZ exhibit hyperactivation of localized prefrontal cortex brain regions and dysfunction of functional connectivity during resting state, which are significantly associated with core clinical symptoms including positive, negative, and excitement/hostility symptoms.
4.The association between prefrontal cortex functional connectivity and clinical symptoms in patients with schizophrenia
Man DONG ; Yang TIAN ; Lifeng WANG ; Bingqian LIU ; Ranran XUE ; Xinxiu HE ; Xia LIU ; Shanling JI ; Hao YU
Chinese Journal of Behavioral Medicine and Brain Science 2025;34(10):905-911
Objective:To investigate the functional characteristics of the prefrontal cortex in patients with schizophrenia (SCZ) during resting state and analyze its association with clinical symptoms.Methods:Twenty-eight hospitalized patients with SCZ (SCZ group) were selected from November 2023 to May 2024, and 28 healthy controls (HC group) were recruited concurrently. By using functional near-infrared spectroscopy (fNIRS) technology, data on the concentration changes of oxygenated hemoglobin (HbO) and deoxygenated hemoglobin (HbR) in the prefrontal cortex during resting state were collected from all subjects to measure cortical hemodynamic activity. Regional activation values and functional connectivity (FC) values among brain areas were analyzed. Clinical symptoms in patients were assessed using the positive and negative syndrome scale (PANSS).SPSS 25.0 software was employed for statistical analysis. Between-group comparisons were performed using independent samples t-tests or Mann-Whitney U tests. Spearman correlation analysis and general linear regression models were applied to examine relationships between prefrontal cortical functional characteristics and clinical symptoms. Results:The levels of HbO in the right inferior frontal gyrus and left frontal pole area were significantly higher in the SCZ group (1.5 (1.0, 3.0)μmol/L, 1.0 (1.0, 2.8)μmol/L) than those in the HC group (-0.01 (-0.05, 0.02)μmol/L, -0.02 (-0.07, 0.03)μmol/L) ( Z=-6.46, -6.50, both P<0.01). The levels of HbR in the bilateral dorsolateral prefrontal cortex were significantly higher in the SCZ group (0.02 (-0.01, 0.07)μmol/L, 0.01 (-0.01, 0.03)μmol/L) than those in the HC group (-0.01 (-0.03, 0.01)μmol/L, -0.01 (-0.02, 0.01)μmol/L) ( Z=-2.46, -1.98, both P<0.05).The SCZ group showed significantly higher HbO-based FC values in the frontal pole-temporal pole (0.49±0.21) and temporal pole-dorsolateral prefrontal cortex (0.36±0.25) compared to the HC group (0.33±0.18, 0.15±0.19) ( t=3.02, 3.44, both P<0.01). Conversely, the SCZ group exhibited significantly lower HbR-based FC in the frontal pole-inferior frontal gyrus (0.15±0.13) and inferior frontal gyrus-temporal pole (0.27±0.37) compared to the HC group (0.33±0.26, 0.77±0.48) ( t=-3.17, -4.23, both P<0.01). Correlation analysis revealed that in the SCZ group, the level of HbO in the right inferior frontal gyrus was positively correlated with negative symptoms, positive symptoms, excitement/hostility, and PANSS total score ( r=0.45-0.64, all P<0.05), and the level of HbO in the left frontal pole area was positively correlated with excitement/hostility and PANSS total score ( r=0.57, 0.50, both P<0.01), while the FC value between the frontal pole and temporal pole areas showed a negative correlation with excitement/hostility ( r=-0.39, P<0.05). Regression analysis demonstrated that, the HbO concentration in the right inferior frontal gyrus significantly positively predicted PANSS total score, positive symptoms, and negative symptoms ( β=0.70, 0.64, 0.55, all P<0.01).The HbO concentration in the left frontal pole area significantly positively predicted excitement/hostility ( β=0.77, P<0.01).The frontal pole-temporal pole HbO-based FC significantly negatively predicted excitement/hostility scores ( β=-0.42, P<0.01). Conclusion:Patients with SCZ exhibit hyperactivation of localized prefrontal cortex brain regions and dysfunction of functional connectivity during resting state, which are significantly associated with core clinical symptoms including positive, negative, and excitement/hostility symptoms.
5.Influence of helical tomography radiotherapy planning parameters on threading effect
Ruo-qi CAO ; Xia-yu HANG ; Hua HUANG ; Xian-qiang SONG ; Jin-da ZHOU ; Yun-jie BAI ; Xiang-dong SUN ; Yi-kun LI
Chinese Medical Equipment Journal 2025;46(8):58-66
Objective To investigate the influence of helical tomographic radiotherapy plans with different combinations of lead gate width,pitch and algorithms on threading effects.Methods A target model was established with a Cheese Phantom used as the simulated human body,then three lead gate widths(1.0,2.5,and 5.0 cm),six screw pitches(0.143,0.172,0.215,0.287,0.430,and 0.500)and two computational grids(Fine algorithm and Normal algorithm)were respectively combined for designing the helical tomography radiotherapy plans.The radiotherapy plans with a pitch of 0.143,0.172,0.215,0.287 or 0.430 were enrolled into an experimental group,and the plans with a pitch of 0.500 were divided into a control group.The dosimetric parameters including maximum dose(Dmax),minimum dose(Dmin)and mean dose(Dmean)of the target area PTV1 and PTV2 were evaluated by the dose volume histogram(DVH).The dose homogeneity index(HI)of the target area was calculated,and the single rotation time and total treatment time of each plan were recorded and counted.SPSS 27.0 software was used for statistical analysis.Results No significant threading effect appeared regardless of the pitch value when the lead gate width was 1.0 cm.The threading effects in the experimental group were weaker than those in the control group when the lead gate width was 2.5 or 5.0 cm.The threading effect gradually rose with the pitch increased when the lead gate width was 5.0 cm.The most significant difference was found between the threading effect in case of the screw pitch being 0.500 and that with the screw pitch being 0.143,with the differenes being statistically obvious(P<0.05).The lead gate width had significant effects on the Dmax,Dmin,Dmean and HI of PTV1 and PTV2.When the lead gate width was 5.0 cm,high HI value and uneven dose distribution were detected and lowered screw pitch weakened the threading effect.The single rotation time first remained constant and then increased with the screw pitch was enlarged,with the changing points occurring in case of the screw pitches of 0.287 and 0.430.With a certain lead gate width,the treatment time for plans was shortened with the decrease of the pitches in case of the pritches lower than 0.287,and tended to be constant after the screw pitches reached 0.287.The changes of the computational grid had no significant effects on the results of radiotherapy plans when the lead gate width and screw pitch were kept constant.Conclusion When designing a spiral tomotherapy plan with conventional doses,a lead gate width of 1.0 or 2.5 cm and a screw pitch of 0.287 or 0.430 should be selected in order to minimize the threading effect while ensuring the efficiency of plan implementation.[Chinese Medical Equipment Journal,2025,46(8):58-66]
6.Chemical constituents from the bark of Toona sinensis and their anti-inflammatory activity
Wei WU ; Shou-mao SHEN ; Yan-ni WANG ; Xia ZHANG ; Jin-yu LI ; Wei-dong PAN
Chinese Traditional Patent Medicine 2025;47(9):2950-2956
AIM To study the chemical constituents from the bark of Toona sinensis(A.Juss.)Roem and their anti-inflammatory activity.METHODS Silica gel,RP-18 reverse phase silica gel and HPLC were used for isolation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activity were evaluated by RAW264.7 model.RESULTS Sixteen compounds were isolated and identified as(9Z)-18-hydroxyo-ctadec-9-en-4,6-diyn-3-one(1),toonapolyyne C(2),(9S,10E,16R)-octadec-10-ene-12,14-diyne-1,9,16-triol(3),(9S,10E,16R)-9,16-dihydroxyoctadec-10-ene-12,14-diy-n-1-yl acetate(4),toonapolyyne A(5),toonasindiyne B(6),scopoletin(7),sco-parone(8),3-O-acetyl(-)-epicatechin(9),p-ethoxyacetanilide(10),kulonic acid(11),β-sitosterol-3-O-β-D-glucopyranoside(12),vanillic acid(13),cleomiscosin A(14),(-)-isolariciresinol(15),resveratrol(16).The IC50 values of compounds 3-4,6,11-13 for NO were 6.90,10.49,20.03,9.49,18.34,24.36 μmol/L,respectively.CONCLUSION Compound 1 is a new polyacetylene,8-16 are isolated from T.sinensis for the first time.Compounds 3-4,6,11-13 have good anti-inflammatory activity.
7.Measurement method based on EBT3 film technology for quality control detection of INTRABEAM PRS500 intraoperative radiotherapy equipment
Yi-kun LI ; Wei DING ; Xia-yu HANG ; Jun HU ; Xiang-dong SUN ; Ai-jun XU
Chinese Medical Equipment Journal 2025;46(6):47-53
Objective To propose an EBT3 film technology-based quality control measurement method for the INTRABEAM PRS500 intraoperative radiotherapy equipment to solve the problems of the traditional methods in cumbersome operation and setup error.Methods According to HJ 1198-2021 Requirements of radiation safety and protection for radiotherapy and GBZ 121-2020 Requirements for radiological protection in radiotherapy,the environmental radiation testing of the INTRABEAM PRS500 intraoperative radiotherapy equipment was carried out point by point by means of the radiation inspection instrument.The INTRABEAM PRS500 intraoperative radiotherapy equipment was characterized by a point X-ray source(XRS),and the XRS was detected in terms of the probe linearity,radiation dose,dynamic deviation,isotropy and dose rate.The EBT3 film technology was used to verify the symmetry and isotropy of the XRS planar dose of INTRABEAM PRS500 intraoperative radiotherapy equipment.Results The X-γ dose equivalent rate of each monitoring site of the INTRABEAM PRS500 intraoperative radiotherapy device was lower than the method detection limit(MDL).The results of SQA quality control showed that the INTRABEAM PRS500 intraoperative radiotherapy equipment XRS met the quality control requirements in terms of the probe linearity,radiation dose,dynamic deviation and etc,and the isotropy differences in the+X,-X,+Y,and-Y axis directions ranged from-1.40%to 1.79%,which were all within the allowable range of measurement tolerance(5.60%to 5.65%).The results of measuring the isotropy of the INTRABEAM PRS500 intraoperative radiotherapy equipment based on the EBT3 film technology showed that the dose distribution of the XRS in the directions of the+X,-X,+Y,and-Y axes at the same plane was well isotropic,and that the doses in the directions of the X and Y axes were symmetrically distributed,and that the maximum skewness value for the isotropy of the XRS in the XY plane was-1.581%,which met the requirements of AAPM TG61 report on the reference dosimetry of low-energy and medium-energy X-rays for radiotherapy and radiobiology of≤±5.3%.Conclusion The EBT3 film technology-based measurement method gains high simplicity and feasibility for the isotropy of the INTRABEAM PRS500 intraoperative radiotherapy equipment in the directions of the+X,-X,+Y,and-Y axes at the same planet,which realizes the dynamic monitoring of the dosimetric changes and facilitates the whole-process quality control management of the intraoperative radiotherapy equipment.[Chinese Medical Equipment Journal,2025,46(6):47-53]
8.Review of prehospital hemostatic devices applied in noncompressible hemorrhage
Fei GAO ; Yu-qing DONG ; Lei XU ; Hong-xia LI
Chinese Medical Equipment Journal 2025;46(6):72-82
The definition and classification of noncompressible hemorrhage were introduced.The current status of the application of prehospital hemostatic devices in noncompressible hemorrhage were reviewed,and the indications and methods of use of various types of devices were analyzed.The existing problems of prehospital hemostatic devices were analyzed,and the future development directions were envisioned.[Chinese Medical Equipment Journal,2025,46(6):72-82]
9.Mechanism of Polygonum capitatum on atherosclerosis based on data mining
Zi YE ; Yun-pei WANG ; Yu-hui WANG ; Xun-de XIAN ; Xiao-jie LI ; Chun-hua HUANG ; Yuan-zhu LIAO ; Di-dong LOU ; Yi-xia ZHOU
Chinese Pharmacological Bulletin 2025;41(12):2369-2378
Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.
10.Application of risk anticipation and coping intervention model in patients undergoing anterior decompression and bone grafting with internal fixation
Yi YU ; Jinmei QI ; Fulong DONG ; Jing ZHANG ; Xia YAN ; Shixin SHENG ; Lili XIA
Chinese Journal of Modern Nursing 2025;31(17):2315-2320
Objective:To explore the application effect of risk anticipation and coping intervention model in patients with cervical spondylosis undergoing anterior decompression and bone grafting with internal fixation.Methods:A convenience sampling method was used to select 132 patients with cervical spondylosis who underwent the aforementioned surgical procedure at the First Affiliated Hospital of Anhui Medical University between January 2022 and June 2024. Patients admitted between January 2022 and March 2023 ( n=66) formed the control group and received routine nursing care, while those admitted between April 2023 and June 2024 ( n=66) formed the observation group and received nursing interventions based on the risk anticipation and coping model. Both groups were followed until three months after discharge. Pain intensity, swallowing function, nutritional status, cervical spine function, and quality of life were compared between the two groups. Results:Pain scores were lower in the observation group than in the control group at 6, 12, 24, and 48 hours postoperatively ( P<0.05) . At 24 and 48 hours postoperatively, the observation group had significantly better scores on the Kubota Water Swallowing Test compared to the control group ( P<0.05) . On the day before discharge and three months post-discharge, body mass index, plasma albumin, total protein, Japanese Orthopaedic Association score, and quality of life score were all significantly higher in the observation group than in the control group ( P<0.05) . Conclusions:The risk anticipation and coping intervention model can effectively reduce postoperative pain and improve swallowing function in patients undergoing anterior decompression and bone grafting with internal fixation for cervical spondylosis. It also promotes the recovery of cervical spine function and enhances quality of life.

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