The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Objective:To observe the therapeutic effect of combining low-frequency pulsed electrical stimulation with Beckman oral muscle exercise training in relieving drooling among persons with Parkinson′s disease (PD).Methods:A random number table was used to divide 120 PD patients with drooling into a mouth muscle training group, an electrical stimulation group, and an observation group, with 40 patients in each group. In addition to routine medication, the oral muscle training group was given Beckman oral muscle exercise training, the electrical stimulation group underwent low-frequency pulsed electrical stimulation treatment, while the observation group was provided with both. Before and after 4 weeks of treatment, the severity of salivation, the frequency of repeated empty swallowing, oral motor function, saliva secretion, and life quality of the three groups were evaluated using the Saliva Rating Scale (DRS), the Repeated Saliva Swallowing Test (RSST), oral motor function grading, the Parkinson′s Disease Saliva Clinical Scale (SCS-PD), saliva weighing, and the PD Quality of Life Scale (PDQ-39).Results:After the treatment the average DRS, SCS-PD, saliva weighing and PDQ-39 results of the observation group were significantly better than those before treatment and better than the other 2 groups′ averages. That group′s average RSST and oral motor function scores had increased significantly compared to before treatment, and compared with the other 2 groups′ averages at the same time point.Conclusions:Combining low-frequency pulsed electrical stimulation with Beckman oral muscle exercise can improve oral motor function, swallowing, and the life quality of PD patients who drool. It is more effective than electrical stimulation or oral muscle exercise training alone. Such combination therapy is worthy of clinical promotion and application.

Objective:To observe the therapeutic effect of combining low-frequency pulsed electrical stimulation with Beckman oral muscle exercise training in relieving drooling among persons with Parkinson′s disease (PD).Methods:A random number table was used to divide 120 PD patients with drooling into a mouth muscle training group, an electrical stimulation group, and an observation group, with 40 patients in each group. In addition to routine medication, the oral muscle training group was given Beckman oral muscle exercise training, the electrical stimulation group underwent low-frequency pulsed electrical stimulation treatment, while the observation group was provided with both. Before and after 4 weeks of treatment, the severity of salivation, the frequency of repeated empty swallowing, oral motor function, saliva secretion, and life quality of the three groups were evaluated using the Saliva Rating Scale (DRS), the Repeated Saliva Swallowing Test (RSST), oral motor function grading, the Parkinson′s Disease Saliva Clinical Scale (SCS-PD), saliva weighing, and the PD Quality of Life Scale (PDQ-39).Results:After the treatment the average DRS, SCS-PD, saliva weighing and PDQ-39 results of the observation group were significantly better than those before treatment and better than the other 2 groups′ averages. That group′s average RSST and oral motor function scores had increased significantly compared to before treatment, and compared with the other 2 groups′ averages at the same time point.Conclusions:Combining low-frequency pulsed electrical stimulation with Beckman oral muscle exercise can improve oral motor function, swallowing, and the life quality of PD patients who drool. It is more effective than electrical stimulation or oral muscle exercise training alone. Such combination therapy is worthy of clinical promotion and application.

Objective To explore the association between dynamic indexes of maternal progesterone in early pregnancy and the average level and growth rate of fetal head circumference(HC)in mid-and late pregnancy.Methods This study adopted a retrospective cohort design and included 255 singleton pregnant women in the maternal and infant cohort of The First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2024.The progesterone levels of their early venous blood were detected and divided into two groups of progesterone trajectories,namely,fluctuating type and increasing type,by morphology.The dynamic indicators of progesterone in early pregnancy were constructed:cumulative dynamic deviation index in the first trimester(CDDI-P1T),gestational age at progesterone peak(GA-PP),and maximal relative progesterone decline in the first trimester(MRD-P1T).The average head circumference level and linear growth rate of the fetuses in the middle and late pregnancy were calculated.Generalized linear regression(GLM)was used to analyze the linear association between progesterone dynamic indicators and head circumference development.The key gestational weeks of progesterone affecting fetal head development were explored by linear regression of gestational weeks.Ordinary least squares(OLS)regression and restricted cubic spline(RCS)plots were used to draw the nonlinear association between progesterone dynamic indicators and head circumference.Results Among the 255 pregnant women included,92.5％of the progesterone trajectories in early pregnancy were fluctuating,and 7.5％were increasing.The growth rates of the increasing progesterone trajectory group were higher in the second and third trimesters than in the fluctuating group,but the differences were not statistically significant(all P＞0.05).GLM analysis showed that for every 1 unit increase in CDDI-P1T,the head circumference in the middle and late pregnancy increased significantly by 1.574 cm and 1.193 cm(Z=3.714,2.885,P＜0.01).The delay of GA-PP was negatively correlated with the head circumference in the middle pregnancy(β=-0.190 cm,95％CI:-0.339--0.041,P=0.010)but positively correlated with the head circumference growth rate in the late pregnancy(β=0.022 cm/week,95％CI:0.003-0.041,P=0.025).A 10％decrease in the decline of CDDI-P1T increased the head circumference in the middle pregnancy by 0.200 cm(95％CI:0.016-0.384,P=0.033),and a 100％decrease in the decline increased the head circumference growth rate in the late pregnancy by 0.201 cm/week(95％CI:0.002-0.399,P=0.048).The analysis of the key time window showed that for every 20 nmol/L increase in progesterone during 9.5-13 weeks of pregnancy,the mid-term head circumference increased by 0.035-0.166 cm(Z=2.452-3.517,allP＜0.05),and the late-term head circumference increased by 0.767 cm during 9-13 weeks of pregnancy(Z=2.452-3.517,all P＜0.05).When progesterone increased during 9.5-10.5 weeks of pregnancy,the growth rate of mid-term head circumference increased by 0.013-0.023 cm/week(Z=2.074-2.243,all P＜0.01).When progesterone increased during 8.5-10.5 weeks of pregnancy,the growth rate of late-term head circumference increased by 0.010-0.026 cm/week(Z=2.061-3.137,all P＜0.05).Conclusion Progesterone dynamic index is a new sensitive tool for evaluating fetal head circumference development.There is a stage-specific window period for progesterone regulation.9.5-13 weeks of pregnancy is the critical period for progesterone to affect head circumference growth,and 9.5-10.5 weeks of pregnancy is the core window for regulating the growth rate of head circumference.Therefore,it is necessary to combine progesterone dynamic index and time window for individualized intervention to promote the transformation of prenatal care from pregnancy maintenance to eugenics intervention.

BACKGROUND:Ankle inversion injuries frequently occur during landing,injuring the anterior talofibular and calcaneofibular ligaments.Previous studies usually used indirect indicators,such as inversion angle,as an injury risk indicator,but epidemiological support is lacking.OBJECTIVE:To calculate anterior talofibular and calcaneofibular ligament strains using a three-dimensional multi-body foot model during a drop-landing and to investigate whether increasing the foot toe-out angle for landing would reduce the risk of inversion sprains.METHODS:Thirty-five participants with high sports demands[15 males and 20 females,age:(21.0±0.9)years,height:(176.2±8.8)cm,body mass:(71.6±12.8)kg]were recruited to perform a drop-landing test using a trapdoor device to simulate ankle inversion sprains.Two landing conditions were tested,i.e.,natural landing and toe-out landing.Kinematic data were collected using a 12-camera motion analysis system,the strains of the anterior talofibular and calcaneofibular ligaments were calculated using a three-dimensional rigid-body foot model.RESULTS AND CONCLUSION:From natural landing to toe-out landing conditions,the anterior talofibular ligament strain decreased[natural landing=(3.57±1.92)％,toe-out landing=(0.36±1.18)％,P＜0.001,Cohen's d=2.01),as was the calcaneofibular ligament strain[natural landing=(1.38±1.80)％,toe-out landing=(0.28±2.29)％,P=0.003,Cohen's d=0.81).It could be concluded that increasing foot toe-out angle reduces anterior talofibular and calcaneofibular ligament strains during drop-landing with ankle inversion,thereby reducing the potential of ankle inversion sprains.

Objective To explore the association between dynamic indexes of maternal progesterone in early pregnancy and the average level and growth rate of fetal head circumference(HC)in mid-and late pregnancy.Methods This study adopted a retrospective cohort design and included 255 singleton pregnant women in the maternal and infant cohort of The First Affiliated Hospital of Xi'an Jiaotong University from January 2015 to December 2024.The progesterone levels of their early venous blood were detected and divided into two groups of progesterone trajectories,namely,fluctuating type and increasing type,by morphology.The dynamic indicators of progesterone in early pregnancy were constructed:cumulative dynamic deviation index in the first trimester(CDDI-P1T),gestational age at progesterone peak(GA-PP),and maximal relative progesterone decline in the first trimester(MRD-P1T).The average head circumference level and linear growth rate of the fetuses in the middle and late pregnancy were calculated.Generalized linear regression(GLM)was used to analyze the linear association between progesterone dynamic indicators and head circumference development.The key gestational weeks of progesterone affecting fetal head development were explored by linear regression of gestational weeks.Ordinary least squares(OLS)regression and restricted cubic spline(RCS)plots were used to draw the nonlinear association between progesterone dynamic indicators and head circumference.Results Among the 255 pregnant women included,92.5％of the progesterone trajectories in early pregnancy were fluctuating,and 7.5％were increasing.The growth rates of the increasing progesterone trajectory group were higher in the second and third trimesters than in the fluctuating group,but the differences were not statistically significant(all P＞0.05).GLM analysis showed that for every 1 unit increase in CDDI-P1T,the head circumference in the middle and late pregnancy increased significantly by 1.574 cm and 1.193 cm(Z=3.714,2.885,P＜0.01).The delay of GA-PP was negatively correlated with the head circumference in the middle pregnancy(β=-0.190 cm,95％CI:-0.339--0.041,P=0.010)but positively correlated with the head circumference growth rate in the late pregnancy(β=0.022 cm/week,95％CI:0.003-0.041,P=0.025).A 10％decrease in the decline of CDDI-P1T increased the head circumference in the middle pregnancy by 0.200 cm(95％CI:0.016-0.384,P=0.033),and a 100％decrease in the decline increased the head circumference growth rate in the late pregnancy by 0.201 cm/week(95％CI:0.002-0.399,P=0.048).The analysis of the key time window showed that for every 20 nmol/L increase in progesterone during 9.5-13 weeks of pregnancy,the mid-term head circumference increased by 0.035-0.166 cm(Z=2.452-3.517,allP＜0.05),and the late-term head circumference increased by 0.767 cm during 9-13 weeks of pregnancy(Z=2.452-3.517,all P＜0.05).When progesterone increased during 9.5-10.5 weeks of pregnancy,the growth rate of mid-term head circumference increased by 0.013-0.023 cm/week(Z=2.074-2.243,all P＜0.01).When progesterone increased during 8.5-10.5 weeks of pregnancy,the growth rate of late-term head circumference increased by 0.010-0.026 cm/week(Z=2.061-3.137,all P＜0.05).Conclusion Progesterone dynamic index is a new sensitive tool for evaluating fetal head circumference development.There is a stage-specific window period for progesterone regulation.9.5-13 weeks of pregnancy is the critical period for progesterone to affect head circumference growth,and 9.5-10.5 weeks of pregnancy is the core window for regulating the growth rate of head circumference.Therefore,it is necessary to combine progesterone dynamic index and time window for individualized intervention to promote the transformation of prenatal care from pregnancy maintenance to eugenics intervention.

BACKGROUND:Ankle inversion injuries frequently occur during landing,injuring the anterior talofibular and calcaneofibular ligaments.Previous studies usually used indirect indicators,such as inversion angle,as an injury risk indicator,but epidemiological support is lacking.OBJECTIVE:To calculate anterior talofibular and calcaneofibular ligament strains using a three-dimensional multi-body foot model during a drop-landing and to investigate whether increasing the foot toe-out angle for landing would reduce the risk of inversion sprains.METHODS:Thirty-five participants with high sports demands[15 males and 20 females,age:(21.0±0.9)years,height:(176.2±8.8)cm,body mass:(71.6±12.8)kg]were recruited to perform a drop-landing test using a trapdoor device to simulate ankle inversion sprains.Two landing conditions were tested,i.e.,natural landing and toe-out landing.Kinematic data were collected using a 12-camera motion analysis system,the strains of the anterior talofibular and calcaneofibular ligaments were calculated using a three-dimensional rigid-body foot model.RESULTS AND CONCLUSION:From natural landing to toe-out landing conditions,the anterior talofibular ligament strain decreased[natural landing=(3.57±1.92)％,toe-out landing=(0.36±1.18)％,P＜0.001,Cohen's d=2.01),as was the calcaneofibular ligament strain[natural landing=(1.38±1.80)％,toe-out landing=(0.28±2.29)％,P=0.003,Cohen's d=0.81).It could be concluded that increasing foot toe-out angle reduces anterior talofibular and calcaneofibular ligament strains during drop-landing with ankle inversion,thereby reducing the potential of ankle inversion sprains.

Objective:To assess the capability of seven reference medical laboratories to detect BCR::ABL1 p210 transcription levels and to compare the results among those laboratories.Methods:The interlaboratory comparison was carried out in two stages. The samples were prepared by the reference laboratory. The quantitative values of BCR::ABL1 p210 of the comparison samples covered 0.001%-0.01%, 0.01%-0.1%, 0.1%-1%, 1%-10% and>10% in each stage. Real-time quantitative PCR (RT-PCR) and dPCR (digital PCR) were used to examine the samples. The conversion factor (CF) was calculated and validated for each laboratory.Results:In the RT-PCR comparison, one laboratory was failed to detect BCR::ABL1 p210 in fourteen samples at the first stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.133-0.338) and 95% limits of agreement within ±5 folds (upper limit 0.147-0.785, lower limit -0.770--0.109), and the corresponding CF values were calculated and validated. In the dPCR comparison, one laboratory did not report results at the second stage. The results of the other six laboratories were qualified with the bias <±1.2 folds (-0.026-0.267) and 95% limits of agreement within±5 folds (upper limit 0.084-0.991, lower limit -0.669--0.135), and the corresponding CF values were calculated and validated. The samples with BCR::ABL1 p210 quantitative values of 0.01%-0.1%, 0.1%-1%, 1%-10% and >10% could be detected by both RT-PCR and qPCR. When the quantitative value of BCR::ABL1 p210 was 0.001%-0.01%, the detection rate of dPCR was higher than that of RT-PCR (85.56% vs. 68.00%).Conclusions:A good consistency is present among various laboratories. The quantitative value of BCR::ABL1 p210 is comparable among laboratories as shown by the CF value conversion. For quantitative detection of BCR::ABL1 p210 deep molecular reaction, dPCR has a higher positive detection rate and more advantages than RT-PCR. To ensure the accuracy and reproducibility of the BCR::ABL1 p210 test, it is imperative for every laboratory to enhance their daily quality control practices.

Objective To explore the regulatory role of hederagenin(HG)on glutamate(Glu)-in-duced ferroptosis and corresponding inflammatory responses in mouse hippocampal neuron HT22 cells and investigate its potential mechanisms.Methods HT22 cells were randomly divided into control,Glu and HG groups(n=3).The cells of the control group received no treatment,the cells of the Glu group were treated with 35 mmol/L Glu for 24 h to establish a cellular model of ferroptosis in Alzheimer's disease,and the cells of the HG group were treated with 0.5 μmol/L HG and 35 mmol/L Glu for 24 h simultaneously.FerroOrange fluorescent probe was used to de-tect intracellular Fe2+.The production of reactive oxygen species(ROS),mitochondrial membrane potential,and levels of inflammatory factors TNF-α,IL-1β and IL-6 in the cells were assessed.Finally,the expression of the key regulator of iron death,glutathione peroxidase 4(GPX4)was measured.Results Compared to the control group,the levels of intracellular Fe2+,ROS,TNF-α,IL-1β,and IL-6 were significantly elevated,while the mitochondrial membrane potential was obvi-ously reduced in the Glu group(P＜0.05,P＜0.01).The HG group had significantly decreased Fe2+,ROS,TNF-α,IL-1β,and IL-6 and enhanced mitochondrial membrane potential than the Glu group(P＜0.05,P＜0.01).The GPX4 expression was significantly lower in the Glu group than the control group(1.00±0.02 vs 0.46±0.04,P＜0.01),and was notably higher in the 0.5 and 1.0 μmol/L HG groups when compared to the Glu group(0.64±0.03 and 0.59±0.05 vs 0.46±0.04,P＜0.01).Conclusion HG inhibits ferroptosis by regulating GPX4 expression,and thereby effec-tively alleviates the inflammatory response.

Objective: To explore the changes in ribosomal DNA copy number in peripheral blood among patients with pneumoconiosis and its influencing factors, so as to provide insights into prevention and treatment of pneumoconiosis. Methods: Eighty-eight patients with pneumoconiosis who visited a designated hospital and 71 community residents with no history of pneumoconiosis or dust exposure were selected as the pneumoconiosis group and control group, and age, smoking history, drinking history and cumulative years of exposure to dust were collected through questionnaire surveys. The copy number of 45S rDNA and 5S rDNA was detected using real-time fluorescence quantitative PCR, and the differences between the two groups were compared. Factors affecting the copy number of 45S rDNA and 5S rDNA were identified by a multiple linear regression model. Results: The pneumoconiosis group had a median age of 56.00 (interquartile range, 15.25) and a mean cumulative dust exposure duration of (12.40±8.08) years, with 56.82% smoking and 62.50% drinking. The control group had a median age of 64.00 (interquartile range, 37.00) years, with 32.39% smoking and 26.76% drinking. The median copy number of 45S rDNA in the pneumoconiosis group was 1.29 (interquartile range, 0.59), which was lower than 2.10 (interquartile range, 1.88) in the control group; the median copy number of 5S rDNA in the pneumoconiosis group was 5.33 (interquartile range, 0.85), which was higher than 4.66 (1.34) in the control group (both P<0.05). Multiple linear regression analysis identified age (β=-0.034) and pneumoconiosis (β=-1.595) as factors affecting 45S rDNA copy number, age (β=-0.013) as a factor affecting 5S rDNA copy number, and age (β=0.018) as a factor affecting 5S rDNA copy number in the pneumoconiosis group (all P<0.05). Conclusions Compared with community residents with no history of pneumoconiosis or dust exposure, the copy number of 45S rDNA in peripheral blood among patients with pneumoconiosis is reduced and the copy number of 5S rDNA is increased.