Abstract Alzheimer′s disease(AD) is a common neurodegenerative disease. It has been found that AD is related to various pathogenic factors such as genetics, cardiovascular and cerebrovascular disease, and excessive phosphorylation of tau protein. However, no definitive conclusions on its pathogenesis have been reached. In this paper, the research progress on the pathogenesis of AD inC.elegansmodel and the therapeutic effects of traditional Chinese medicine extracts on AD are reviewed, providing a basis for further research on the alleviating effects of Chinese medicine extracts on AD.

Objective To compare the success rate and stability of rat models of comorbid chronic pain and depression induced by different doses of complete Freund's adjuvant(CFA).Methods Sixty SD rats were divided randomly into a control group,low-dose CFA group(CFA-L),and high-dose CFA group(CFA-H)(n=20 rats per group).Rats in the CFA-L and CFA-H groups were injected with 50 and 100 μL CFA,respectively,and rats in the control group were injected with 0.9％sodium chloride solution.The general state,body weight,mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were observed at 0,7,14,21,and 28 days after modeling.Depressive behavior was evaluated using the open field test(OFT),forced swim test(FST),and tail suspension test(TST).Glutamate(Glu)and γ-aminobutyric acid(GABA)levels in the anterior cingulate cortex were detected by enzyme-linked immunosorbent assay.Brain-derived neurotrophic factor(BDNF)expression in the anterior cingulate cortex was detected by immunohistochemistry,and pathological changes in the anterior cingulate cortex were observed by HE staining.Results(1)Regarding the general condition of the rats,the left ankle joint and toes were obviously red and swollen in the CFA-L and CFA-H groups on the 7th day after modeling,and the swelling was more severe in the CFA-H group.The redness and swelling of the left hind foot and ankle joint and toes gradually recovered in the CFA-L group on days 14,21,and 28 after modeling,but were still obvious in the CFA-H group,and the water and food intake decreased.(2)The body mass was significantly lower in rats in the CFA-H group compared with those in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05).(3)Regarding pain-related behavior,the MWT and TWL were significantly decreased in the CFA-L and CFA-H groups on the 7th and 14th days after modeling,compared with the control group(P＜0.05,P＜0.05).On day 21 after modeling,MWT was significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),and TWL was significantly lower in the CFA-L and CFA-H groups than in the blank group(P＜0.05,P＜0.05).On day 28 after modeling,MWT and TWL were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05).(4)In terms of depression-related behaviors,the total OFT movement distance was significantly lower in the CFA-H group than in the blank and CFA-L groups on day 7 after modeling(P＜0.05,P＜0.05).The total OFT distance and central dwell time were significantly lower in the CFA-H group than in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05),and the result in the FST and TST were significantly higher than in the blank and CFA-L groups(P＜0.05,P＜0.05).(5)Glu,GABA,and BDNF expression levels were significantly higher in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),while GABA,Glu/GABA,and BDNF levels were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05,P＜0.05).(6)The CFA-L group showed less damage in the anterior cingulate cortex,more pyramidal cells,more arranged cells,clear nucleoli,and a small number of cells with karyokynesis and deep staining.Compared with the CFA-L group,rats in the CFA-H group showed a disordered cell arrangement in the injured area of the anterior cingulate cortex,a large number of pyknotic and hyperchromatic neurons,significantly fewer or absent pyramidal cells,and vacuoles,red blood cells,and neurofibrillary tangles in the interstitial space.Conclusions Injection of CFA 100 μL can be used to establish a rat model of chronic inflammatory pain and depression,showing hyperalgesia,depression-like behavioral changes,changes in levels of Glu,GABA,and BDNF in the anterior cingulate cortex,and pathological changes in the anterior cingulate cortex,consistent with the pathophysiological characteristics of chronic pain and depression.

Objective To establish a foot-weightlifting shoe coupling model,investigate the biomechanical effects of midsole material variations during pull phase of the snatch,optimize the key parameters of weightlifting shoes,and reduce the risk of foot and ankle injuries in athletes.Methods The foot-weightlifting shoe finite element model was constructed using the finite element method for simulation.Kinematic and dynamic data of the snatch movement were obtained using the sports biomechanics methods.Statistical methods were employed to validate the effectiveness of the model and compare the impact of different midsole materials on foot stress distribution,bone stress,soft tissue stress,and midsole strain of the athletes during pull phase of the snatch.Results When the midsole thermoplastic polyurethane(TPU)had an elastic modulus of 20 MPa,the peak foot stress was minimized.As the elastic modulus of the midsole TPU increased,the foot peak stress also increased.Bone stress was concentrated in the third,fourth,and fifth metatarsals of the forefoot,with the fourth metatarsal showing the peak stress.As the elastic modulus of the midsole increased,the peak stress in the metatarsal area gradually decreased,the peak stress in soft tissues gradually increased,and the strain in midsole decreased.Conclusions Medium-hardness midsole materials(with an elastic modulus between 20-25 MPa)have an advantage in reducing foot pressure and preventing bone injuries in the foot and ankle.

Objectives:To investigate the effect of non-optimal temperature exposure during pregnancy on the risk for preterm birth and identify the susceptible exposure window. At the same time, the interaction between non-optimal temperature and pollutants exposure during pregnancy on preterm birth was analyzed, in order to provide strong clues for the influence of non-optimal temperature exposure during pregnancy on the risk for preterm birth.Methods:A total of 1 852 pregnant women were recruited from September 2021 to June 2023 in Fujian Provincial Maternal and Child Health Care Center. Questionnaire survey was conducted, and their health records were analyzed. The permanent address of each pregnant woman was matched with Fifth Generation European Centre for Medium-Range Weather Forecasts Atmospheric Reanalysis of the Global Climate and a geo-statistical combination model based on satellite remote sensing data collection, then follow-up for pregnancy outcome was conducted. Distributed lag nonlinear model was used to assess the association between exposure to non-optimal temperature during pregnancy and the risk for preterm birth and a multiplicative interaction model was used to assess the interaction between exposure to pollutants and non-optimal temperatures during pregnancy on the risk for preterm birth.Results:After adjusting for potential confounders such as maternal age, occupation, Gross Domestic Product of the region, pre-pregnancy preconception BMI, newborn sex, the weekly susceptibility windows of extreme low temperature ( P1, P3, P5) were week 1-22 , and the weekly susceptibility windows of extreme high temperature ( P95, P97, P99) were week 27 and week 32-36. Extreme low temperature [ P1 ( OR=1.147, 95% CI: 1.041-1.265), P5 ( OR=1.284, 95% CI: 1.035-1.501)] and extreme high temperature [ P97 ( OR=1.146, 95% CI: 1.039-1.263), P99 ( OR=1.216, 95% CI: 1.099-1.345)] exhibited multiplicative interaction with PM 2.5. Conclusions:Exposure to non-optimal temperature during pregnancy was associated with an increased risk for preterm birth. The susceptible exposure windows of extreme low temperature were mainly in early and mid-pregnancy, and the susceptible exposure windows of extreme high temperature were mainly in late-pregnancy. Exposure to non-optimal temperatures and pollutants during pregnancy was associated with an increased risk for preterm birth.

Objectives:To investigate the effect of non-optimal temperature exposure during pregnancy on the risk for preterm birth and identify the susceptible exposure window. At the same time, the interaction between non-optimal temperature and pollutants exposure during pregnancy on preterm birth was analyzed, in order to provide strong clues for the influence of non-optimal temperature exposure during pregnancy on the risk for preterm birth.Methods:A total of 1 852 pregnant women were recruited from September 2021 to June 2023 in Fujian Provincial Maternal and Child Health Care Center. Questionnaire survey was conducted, and their health records were analyzed. The permanent address of each pregnant woman was matched with Fifth Generation European Centre for Medium-Range Weather Forecasts Atmospheric Reanalysis of the Global Climate and a geo-statistical combination model based on satellite remote sensing data collection, then follow-up for pregnancy outcome was conducted. Distributed lag nonlinear model was used to assess the association between exposure to non-optimal temperature during pregnancy and the risk for preterm birth and a multiplicative interaction model was used to assess the interaction between exposure to pollutants and non-optimal temperatures during pregnancy on the risk for preterm birth.Results:After adjusting for potential confounders such as maternal age, occupation, Gross Domestic Product of the region, pre-pregnancy preconception BMI, newborn sex, the weekly susceptibility windows of extreme low temperature ( P1, P3, P5) were week 1-22 , and the weekly susceptibility windows of extreme high temperature ( P95, P97, P99) were week 27 and week 32-36. Extreme low temperature [ P1 ( OR=1.147, 95% CI: 1.041-1.265), P5 ( OR=1.284, 95% CI: 1.035-1.501)] and extreme high temperature [ P97 ( OR=1.146, 95% CI: 1.039-1.263), P99 ( OR=1.216, 95% CI: 1.099-1.345)] exhibited multiplicative interaction with PM 2.5. Conclusions:Exposure to non-optimal temperature during pregnancy was associated with an increased risk for preterm birth. The susceptible exposure windows of extreme low temperature were mainly in early and mid-pregnancy, and the susceptible exposure windows of extreme high temperature were mainly in late-pregnancy. Exposure to non-optimal temperatures and pollutants during pregnancy was associated with an increased risk for preterm birth.

Objective To compare the success rate and stability of rat models of comorbid chronic pain and depression induced by different doses of complete Freund's adjuvant(CFA).Methods Sixty SD rats were divided randomly into a control group,low-dose CFA group(CFA-L),and high-dose CFA group(CFA-H)(n=20 rats per group).Rats in the CFA-L and CFA-H groups were injected with 50 and 100 μL CFA,respectively,and rats in the control group were injected with 0.9％sodium chloride solution.The general state,body weight,mechanical withdrawal threshold(MWT),and thermal withdrawal latency(TWL)were observed at 0,7,14,21,and 28 days after modeling.Depressive behavior was evaluated using the open field test(OFT),forced swim test(FST),and tail suspension test(TST).Glutamate(Glu)and γ-aminobutyric acid(GABA)levels in the anterior cingulate cortex were detected by enzyme-linked immunosorbent assay.Brain-derived neurotrophic factor(BDNF)expression in the anterior cingulate cortex was detected by immunohistochemistry,and pathological changes in the anterior cingulate cortex were observed by HE staining.Results(1)Regarding the general condition of the rats,the left ankle joint and toes were obviously red and swollen in the CFA-L and CFA-H groups on the 7th day after modeling,and the swelling was more severe in the CFA-H group.The redness and swelling of the left hind foot and ankle joint and toes gradually recovered in the CFA-L group on days 14,21,and 28 after modeling,but were still obvious in the CFA-H group,and the water and food intake decreased.(2)The body mass was significantly lower in rats in the CFA-H group compared with those in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05).(3)Regarding pain-related behavior,the MWT and TWL were significantly decreased in the CFA-L and CFA-H groups on the 7th and 14th days after modeling,compared with the control group(P＜0.05,P＜0.05).On day 21 after modeling,MWT was significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),and TWL was significantly lower in the CFA-L and CFA-H groups than in the blank group(P＜0.05,P＜0.05).On day 28 after modeling,MWT and TWL were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05).(4)In terms of depression-related behaviors,the total OFT movement distance was significantly lower in the CFA-H group than in the blank and CFA-L groups on day 7 after modeling(P＜0.05,P＜0.05).The total OFT distance and central dwell time were significantly lower in the CFA-H group than in the blank and CFA-L groups on days 14,21,and 28 after modeling(P＜0.05,P＜0.05),and the result in the FST and TST were significantly higher than in the blank and CFA-L groups(P＜0.05,P＜0.05).(5)Glu,GABA,and BDNF expression levels were significantly higher in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05),while GABA,Glu/GABA,and BDNF levels were significantly lower in the CFA-H group than in the blank and CFA-L groups(P＜0.05,P＜0.05,P＜0.05).(6)The CFA-L group showed less damage in the anterior cingulate cortex,more pyramidal cells,more arranged cells,clear nucleoli,and a small number of cells with karyokynesis and deep staining.Compared with the CFA-L group,rats in the CFA-H group showed a disordered cell arrangement in the injured area of the anterior cingulate cortex,a large number of pyknotic and hyperchromatic neurons,significantly fewer or absent pyramidal cells,and vacuoles,red blood cells,and neurofibrillary tangles in the interstitial space.Conclusions Injection of CFA 100 μL can be used to establish a rat model of chronic inflammatory pain and depression,showing hyperalgesia,depression-like behavioral changes,changes in levels of Glu,GABA,and BDNF in the anterior cingulate cortex,and pathological changes in the anterior cingulate cortex,consistent with the pathophysiological characteristics of chronic pain and depression.

Objective To establish a foot-weightlifting shoe coupling model,investigate the biomechanical effects of midsole material variations during pull phase of the snatch,optimize the key parameters of weightlifting shoes,and reduce the risk of foot and ankle injuries in athletes.Methods The foot-weightlifting shoe finite element model was constructed using the finite element method for simulation.Kinematic and dynamic data of the snatch movement were obtained using the sports biomechanics methods.Statistical methods were employed to validate the effectiveness of the model and compare the impact of different midsole materials on foot stress distribution,bone stress,soft tissue stress,and midsole strain of the athletes during pull phase of the snatch.Results When the midsole thermoplastic polyurethane(TPU)had an elastic modulus of 20 MPa,the peak foot stress was minimized.As the elastic modulus of the midsole TPU increased,the foot peak stress also increased.Bone stress was concentrated in the third,fourth,and fifth metatarsals of the forefoot,with the fourth metatarsal showing the peak stress.As the elastic modulus of the midsole increased,the peak stress in the metatarsal area gradually decreased,the peak stress in soft tissues gradually increased,and the strain in midsole decreased.Conclusions Medium-hardness midsole materials(with an elastic modulus between 20-25 MPa)have an advantage in reducing foot pressure and preventing bone injuries in the foot and ankle.

Objective To present and discuss beam characteristics of the first Mevion S250i gantry-mounted accelerator pencil beam scanning proton therapy system in China.Methods The output dose was measured using a parallel-plate ionization chamber.The integrated depth dose was measured with a large-radius Bragg peak ionization chamber,covering 19 energy levels ranging from 227 MeV to 28 MeV,to analyze the proton beam characteristics.The spots in the air were measured with Phoenix flat panel detector on the beam central axis,and the precision of the delivery position was verified by measuring the multi-spot beam map.The interleaf leakage and penumbra reduction of adaptive aperture were measured to characterize its performance.Results The proton system was calibrated for a maximum energy of 227 MeV,with a(10×10)cm2uniform field delivering 1 Gy dose at a depth of 5 cm underwater.The system effectively modulated the proton beam range to the patient's surface,maintaining a constant 80%-80%Bragg peak width of 8.6 mm at all energy levels.The spot size of the highest energy beam at the isocenter was about 4 mm in the air,and the spot delivery position error was less than 1 mm.The interleaf leakage rate of the adaptive aperture for the highest energy beam was below 1.5%,and the penumbra was significantly reduced.Conclusion Mevion S250i proton therapy system demonstrates unique design and beam characteristics,which is reflected in the Bragg peak shape,spot size variation with energy,and penumbra sharpening of adaptive aperture;and these differences should be considered in treatment planning system modeling and planning for precision treatment.

Endometriosis(EMs)is a chronic inflammatory disease.It has been proved that inflammatory microenvironment is the key role in EMs occurance and development.Chinese medicine posits that the theory of"same disease of blood and water",which generally refers to"intermingling dampness and blood stasis",serves as a crucial pathogenesis in EMs.The inflammatory microenvironment is the main manifestation of dampness and blood stasis in EMs,while the insufficiency of vital qi results in endogenous dampness.The stagnation of blood stasis serves as the foundation for the formation of intermingling dampness and blood stasis.Based on contemporary theories in molecular biology,the macrophage-mediated inflammatory microenvironment serves as the foundation for the formation of dampness,while the participation of macrophages in angiogenesis is crucial for the formation of blood stasis.Investigating the intrinsic connection between the inflammatory microenvironment in EMs and the theory of"same disease of blood and water"can contribute to a better understanding of the pathogenesis of EMs from a novel perspective.Remodeling of the inflammatory microenvironment in endometriosis by targeting macrophages may provide a new strategy for EMs treatment.

Objective:To measure and assess relevant radiation doses at the radiotherapy site of the first domestic single-vault proton therapy system.Methods:The radiation levels of the therapy system during and after beam irradiation were measured, and annual effective doses were assessed for personnel at the site.Results:During beam irradiation, the highest radiation dose was detected at the shielded door of the equipment floor, with a gamma radiation level of 2.140 μSv/h and a neutron radiation level of 0.850 μSv/h. Neutron radiation disappeared immediately once the beams stopped. In contrast, the radiation activated originated mostly from gamma rays. A longer time after beams stopped was associated with lower induced radiation intensity at the same location. Furthermore, a farther distance from the irradiated object corresponded to lower induced radiation intensity at the same time. The assessment result reveal that the annual effective doses to the personnel were at the safe level, with physicists exposed to the highest dose of 2.138 mSv.Conclusions:The radiation level at the studied proton therapy site meets the safety requirement, and the treatment can be performed safely at this site.