Objective To investigate the changes in eosinophil counts and the activation of microglial cells in the brain tissues of mice at different stages of Angiostrongylus cantonensis infection, and to examine the role of microglia in regulating the progression of angiostrongyliasis and unravel the possible molecular mechanisms. Methods Fifty BALB/c mice were randomly divided into the control group and the 7-d, 14-d, 21-day and 25-d infection groups, of 10 mice in each group. All mice in infection groups were infected with 30 stage III A. cantonensis larvae by gavage, and animals in the control group was given an equal amount of physiological saline. Five mice were collected from each of infection groups on days 7, 14, 21 d and 25 d post-infection, and 5 mice were collected from the control group on the day of oral gavage. The general and focal functional impairment was scored using the Clark scoring method to assess the degree of mouse neurological impairment. Five mice from each of infection groups were sacrificed on days 7, 14, 21 d and 25 d post-infection, and 5 mice from the control group were sacrificed on the day of oral gavage. Mouse brain tissues were sampled, and the pathological changes of brain tissues were dynamically observed using hematoxylin and eosin (HE) staining. Immunofluorescence staining with eosinophilic cationic protein (ECP) and ionized calcium binding adaptor molecule 1 (Iba1) was used to assess the degree of eosinophil infiltration and the counts of microglial cells in mouse brain tissues in each group, and the morphological parameters of microglial cells (skeleton analysis and fractal analysis) were quantified by using Image J software to determine the morphological changes of microglial cells. In addition, the expression of M1 microglia markers Fcγ receptor III (Fcgr3), Fcγ receptor IIb (Fcgr2b) and CD86 antigen (Cd86), M2 microglia markers Arginase 1 (Arg1), macrophage mannose receptor C-type 1 (Mrc1), chitinase-like 3 (Chil3), and phagocytosis genes myeloid cell triggering receptor expressed on myeloid cells 2 (Trem2), CD68 antigen (Cd68), and apolipoprotein E (Apoe) was quantified using real-time quantitative reverse transcription PCR (RT-qPCR) assay in the mouse cerebral cortex of mice post-infection. Results A large number of A. cantonensis larvae were seen on the mouse meninges surface post-infection, and many neuronal nuclei were crumpled and deeply stained, with a large number of bleeding points in the meninges. The median Clark scores of mouse general functional impairment were 0 (interquartile range, 0), 0 (interquartile range, 0.5), 6 (interquartile range, 1.0), 14 (interquartile range, 8.5) points and 20 (interquartile range, 9.0) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.45, P < 0.01), and the median Clark scores of mouse focal functional impairment were 0 (interquartile range, 0), 2 (interquartile range, 2.5), 7 (interquartile range, 3.0), 18 (interquartile range, 5.0) points and 25 (interquartile range, 6.5) points in the control group and the 7-d, 14-d, 21-d and 25-d groups, respectively (H = 22.72, P < 0.01). The mean scores of mice general and focal functional impairment were all higher in the infection groups than in the control group (all P values < 0.05). Immunofluorescence staining showed a significant difference in the eosinophil counts in mouse brain tissues among the five groups (F = 40.05, P < 0.000 1), and the eosinophil counts were significantly higher in mouse brain tissues in the 14-d (3.08 ± 0.78) and 21-d infection groups (5.97 ± 1.37) than in the control group (1.00 ± 0.28) (both P values < 0.05). Semi-quantitative analysis of microglia immunofluorescence showed a significant difference in the counts of microglial cells among the five groups (F = 17.66, P < 0.000 1), and higher Iba1 levels were detected in mouse brain tissues in 14-d (5.75 ± 1.28), 21-d (6.23 ± 1.89) and 25-d infection groups (3.70 ± 1.30) than in the control group (1.00 ± 0.30) (all P values < 0.05). Skeleton and fractal analyses showed that the branch length [(162.04 ± 34.10) μm vs. (395.37 ± 64.11) μm; t = 5.566, P < 0.05] and fractal dimension of microglial cells (1.30 ± 0.01 vs. 1.41 ± 0.03; t = 5.266, P < 0.05) were reduced in mouse brain tissues in the 21-d infection group relative to the control group. In addition, there were significant differences among the 5 groups in terms of M1 and M2 microglia markers Fcgr3 (F = 48.34, P < 0.05), Fcgr2b (F = 55.46, P < 0.05), Cd86 (F = 24.44, P < 0.05), Arg1 (F = 31.18, P < 0.05), Mrc1 (F = 15.42, P < 0.05) and Chil3 (F = 24.41, P < 0.05), as well as phagocytosis markers Trem2 (F = 21.19, P < 0.05), Cd68 (F = 43.95, P < 0.05) and Apoe (F = 7.12, P < 0.05) in mice brain tissues. Conclusions A. cantonensis infections may induce severe pathological injuries in mouse brain tissues that are characterized by massive eosinophil infiltration and persistent activation of microglia cells, thereby resulting in progressive deterioration of neurological functions.

ObjectivesTo analyze the trends in mortality and disease burden of colorectal cancer (CRC) among the registered residents in Danyang City, Jiangsu Province, from 2013 to 2023, and to provide a scientific basis for developing CRC prevention and control strategies. MethodsMortality surveillance data on CRC among the registered residents in Danyang City from 2013 to 2023 were collected and analyzed. Crude mortality rate (CMR), age-standardized mortality rate (ASMR), years of life lost (YLL) due to premature death, and YLL rate were calculated. The annual percentage change (APC) and average annual percent change (AAPC) of CMR, ASMR and YLL rate were calculated with Joinpoint Regression Program 4.9.0.1. ResultsA total of 1 920 deaths from colorectal cancer were recorded in Danyang City during 2013‒2023, with an average annual CMR of 21.75/100 000, which showed an upward trend (APC=6.47%, 95%CI: 4.21%‒8.79%, P<0.001), with higher CMR observed in males than that in females. The overall ASMR by Chinese standard population was 12.10/100 000, with no obvious temporal trends (APC=1.37%, P=0.364). ASMR increased with age, particularly after 45 years. The total YLL due to CRC was 34 711 person-years, with an average YLL rate of 3.93‰. The YLL rate showed a significant upward trend from 2013 to 2023 (APC=4.96%, 95%CI: 4.08%‒18.16%, P<0.001) in Danyang City. ConclusionThe mortality rate of colorectal cancer in Danyang City is relatively high and has shown a rising trend, resulting in an increasing disease burden on the residents year by year. Continued efforts to strengthen CRC prevention and control are needed, particularly targeting males and the elderly population.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

The plant F-box protein more axillary growth 2 (MAX2) is a key factor in the signal transduction of strigolactones (SLs) and karrinkins (KARs). As the main component of the SKP1-CUL1-FBX (SCF) complex ubiquitin ligase E3, MAX2 is responsible for specifically recognizing the target proteins, suppressor of MAX2 1/SMAX1-like proteins (SMAX1/SMXLs), which would be degraded after ubiquitination. It can thereby regulate plant morphogenesis and stress responses. There exist homologous genes of MAX2 in the important grain and oil crop soybean (Glycine max). However, its role in plant defense responses has not been investigated yet. Here, GmMAX2b, a homologous gene of MAX2, was successfully cloned from stressed soybean. Bioinformatics analysis revealed that there were two MAX2 homologous genes, GmMAX2a and GmMAX2b, with a similarity of 96.2% in soybean. Their F-box regions were highly conserved. The sequence alignment and cluster analysis of plant MAX2 homologous proteins basically reflected the evolutionary relationship of plants and also suggested that soybean MAX2 might be a multifunctional protein. Expression analysis showed that plant pathogen infection and salicylic acid treatment induced the expression of GmMAX2b in soybean, which is consistent with that of MAX2 in Arabidopsis. Ectopic expression of GmMAX2b compensated for the susceptibility of Arabidopsis max2-2 mutant to pathogen, indicating that GmMAX2b positively regulated plant disease resistance. In addition, yeast two hybrid technology was used to explore the potential target proteins of GmMAX2b. The results showed that GmMAX2b interacted with SMXL6 and weakly interacted with SMXL2. In summary, GmMAX2b is a positive regulator in plant defense responses, and its expression is induced by pathogen infection and salicylic acid treatment. GmMAX2b might exert its effect through interaction with SMXL6 and SMXL2. This study expands the theoretical exploration of soybean disease resistant F-box and provides a scientific basis for future soybean disease resistant breeding.
Glycine max/metabolism* ; Disease Resistance/genetics* ; Plant Diseases/immunology* ; Plant Proteins/genetics* ; Cloning, Molecular ; Gene Expression Regulation, Plant ; F-Box Proteins/genetics* ; Arabidopsis/genetics* ; Phylogeny

Objective To analyze trends in the disease burden of esophageal cancer attributable to high body mass index (BMI) in the Chinese and United States populations from 1990 to 2019 and predict deaths over the next 10 years. Methods This study used Global Burden of Disease 2019 data to obtain mortality and disability-adjusted life-year (DALY) data by year, gender, and age for the disease burden of esophageal cancer attributable to high BMI in China and the United States from 1990 to 2019. Joinpoint regression analysis was conducted to analyze long-term trends. Bayesian age–period–cohort analysis was used to predict age-standardized mortality attributable to esophageal cancer in 2020–2030. Results From 1990 to 2019, the age-standardized mortality rate for esophageal cancer attributable to high BMI in China increased from 1.44/10⁵ to 1.80/10⁵ and the age-standardized DALY rate increased from 34.17/10⁵ to 40.79/10⁵. From the perspective of gender, the number of deaths, DALYs, and the corresponding age-standardized rate of males in China and the United States increased from 1990 to 2019. The age-standardized mortality and DALY rates of Chinese women showed a downward trend, decreasing by 21.36/10⁵ and 29.71/10⁵, respectively. Joinpoint analysis results revealed that the average annual percentage changes (AAPCs) in mortality attributable to esophageal cancer in the total population and men in China from 1990 to 2019 increased by 0.78% (95%CI: 0.71-0.84) and 1.52% (95%CI: 1.44-1.60), respectively, and that in females decreased by 0.88% (95%CI: −0.96-−0.80). AAPC in women in the United States rose at a slow rate of 0.07% (95%CI: 0.02-0.09). The burden of esophageal cancer deaths attributable to high BMI is predicted to continue to rise in China and the United States in 2020–2030. Conclusion The disease burden of esophageal cancer attributable to high BMI significantly increased in China from 1990 to 2019. The disease burden of esophageal cancer caused by high BMI in China is expected to increase from 2020 to 2030.

OBJECTIVE To systematically evaluate the efficacy and safety of thalidomide combined with aclacinomycin， granulocyte colony-stimulating factor and cytarabine （CAG） regimen in the treatment of elderly patients with acute myeloid leukemia （AML）. METHODS CNKI， Wanfang data， VIP， Sino Med， PubMed， Embase， the Cochrane Library and Web of Science were searched comprehensively from the inception to Aug. 27th， 2023. Randomized controlled trials （RCTs） about thalidomide combined with CAG regimen （trial group） versus CAG regimen （control group） in the treatment of elderly AML patients were collected， and RevMan 5.3 software was used for meta-analysis of included studies. RESULTS Finally， 7 RCTs were included， with a total of 601 patients， including 307 patients in the trial group and 294 patients in the control group. Meta-analysis results showed that the trial group was superior to the control group in enhancing the overall response rate [Z＝4.75， P＜0.000 01， OR＝2.80， 95%CI （1.83，4.28）]， complete remission rate [Z＝2.82， P＝0.005， OR＝1.61， 95%CI （1.16， 2.25）]， and improving platelet count [Z＝2.70， P＝0.007， MD＝64.02， 95%CI （17.53， 110.51）]， vascular endothelial growth factor [Z＝13.63，P＜0.000 01， MD＝－65.17， 95%CI（－74.54， －55.80）]， vascular endothelial growth factor receptor [Z＝12.03， P＜ 0.000 01， MD＝－499.01， 95%CI （－580.31， －417.71）] and basic fibroblast growth factor [Z＝4.17， P＜0.000 1，MD＝－0.23， 95%CI（－0.35， －0.12）]. And there was no statistical difference between the trial group and the control group in the incidence of adverse drug reaction [Z＝0.99， P＝0.32， OR＝0.52， 95%CI（0.14，1.89）]， nausea and vomiting [Z＝ 1.06， P＝0.29， OR＝0.66， 95%CI （0.30，1.43）]， constipation or diarrhea [Z＝0.92， P＝0.36， OR＝0.65， 95%CI（0.26， 1.63）]， drowsiness [Z＝1.38， P＝0.17， OR＝0.57， 95%CI（0.26， 1.27）] or myelosuppression [Z＝0.88，P＝0.38，OR＝0.68，95%CI（0.28， 1.62）]. CONCLUSIONS The combination of thalidomide and CAG regimen in the treatment of elderly AML patients can significantly improve clinical efficacy and has high safety.

Objective:To conduct comparative analysis of lung cancer incidence and mortality, as well as long-term trends in incidence and mortality rates and risk factors in China and the United States from 1990 to 2019 based on data from the Global Burden of Disease Study 2019 (GBD 2019) .Methods:The GBD 2019 database was used to extract new lung cancer cases, deaths, and age-standardized rate data for the analysis of lung cancer incidence and deaths in China and the United States based on different sex and age groups from 1990 to 2019. Joinpoint software was used to calculate and analyze annual percentage change (APC) and average annual percentage change (AAPC) of age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of lung cancer in China and the United States from 1990 to 2019, and to analyze the long-term trends. Risk factors associated with lung cancer mortality in China and the United States were analyzed using the disability-adjusted life years (DALYs) .Results:New cases of lung cancer in China increased from 257 000 cases in 1990 to 832 900 cases in 2019, and ASIR increased from 30.20/100 000 in 1990 to 41.71/100 000 in 2019; deaths increased from 256 300 cases in 1990 to 757 200 cases in 2019, and ASMR increased from 31.18/100 000 in 1990 to 38.70/100 000 in 2019. ASIR and ASMR for lung cancer in the United States showed a decreasing trend from 1990 to 2019, with ASIR decreasing from 58.87/100 000 in 1990 to 45.13/100 000 in 2019, and ASMR decreasing from 49.35/100 000 in 1990 to 36.11/100 000 in 2019. In terms of gender, the disease burden of lung cancer in Chinese males was higher than that of females in 1990 and 2019, with new cases of lung cancer in males rising from 179 000 in 1990 to 576 200 in 2019, and ASIR rising from 44.29/100 000 in 1990 to 61.74/100 000 in 2019, mortality rising from 177 900 in 1990 to 523 200 in 2019, and ASMR rising from 46.33/100 000 in 1990 to 58.10/100 000 in 2019. The number of new cases of lung cancer in Chinese females rose from 78 100 in 1990 to 256 700 in 2019, and ASIR rose from 18.01/100 000 in 1990 to 24.76/100 000 in 2019; the number of deaths rose from 78 400 in 1990 to 234 000 in 2019, and ASMR rose from 18.63/100 000 in 1990 to 22.86/100 000 in 2019. In 2019, lung cancer incidence rates for males and females in China and the United States showed an increasing and then decreasing trend with age, with incidence rates of lung cancer in Chinese males and females peaking in the age group of 85-89 years old; and in the United States, incidence rates of lung cancer in males peaked in the age group of 85-89 years old, and incidence rates of females peaked in the age group of 80-84 years old. In 2019, it was shown that mortality rate of lung cancer among males in China increased and then decreased with age, reaching a peak in the age group of 85-89 years old, and mortality rate of lung cancer among females increased with age, reaching a peak in the age group of ≥95 years old. In the United States, lung cancer mortality rate for males and females showed an increasing and then decreasing trend with age, peaking in the 85-89 and 80-84 age groups, respectively. Incidence and mortality rates were higher for males than females in all age groups in China and the United States in 1990 and 2019. The analysis results of Joinpoint software showed that ASIR and ASMR of lung cancer in China showed an overall increasing trend from 1990 to 2019, with an AAPC of 1.16% (95% CI: 0.93%-1.38%, P<0.001) for ASIR and 0.78% (95% CI: 0.56%-1.01%, P<0.001) for ASMR, with the most obviously increasing trend in ASIR and ASMR from 1997 to 2004, the APC were 2.84% and 2.58%, respectively. Lung cancer ASIR and ASMR in the United States population showed a decreasing trend, with an AAPC of -1.08% (95% CI: -1.20%-0.96%, P<0.001) for ASIR and -1.05% (95% CI: -1.24%--0.87%, P<0.001) for ASMR. In 1990 and 2019, the major mortality-related risk factor for lung cancer in China and the United States was smoking, and the major mortality-related risk factor for lung cancer in Chinese females was environmental particulate matter pollution. Conclusion:ASIR and ASMR of lung cancer in China show an increasing trend from 1990 to 2019, and ASIR and ASMR of lung cancer in the United States show a decreasing trend. In 2019, incidence rate of lung cancer in males and females in China show an increasing and then decreasing trend with age, mortality rate of lung cancer for males show an increasing and then decreasing trend with age, and mortality rate of lung cancer for females show an increasing trend with age. Lung cancer incidence and mortality rates for males and females in the United States in 2019 show an increasing and then decreasing trend with age. In both 1990 and 2019, incidence rates and mortality rates are higher for males than for females in all age groups in both China and the United States. Smoking is the major mortality-related risk factor for lung cancer in China and the United States, and environmental particulate matter pollution is the major mortality-related risk factor for lung cancer in Chinese females.

Objective To investigate whether curcumin alleviates septic lung injury by inhibiting ferroptosis through modulating the TXNIP/TRX-1/GPX4 pathway.Methods Male C57BL/6 mice were randomly divided into Sham group,cecal ligation puncture(CLP)-induced sepsis group,CLP with curcumin treatment(50,100,and 200 mg/kg)groups,and CLP with both curcumin(200 mg/kg)and TRX-1 inhibitor PX-12(25 mg/kg)treatment group.Inflammatory factors,MDA,MPO,and GSH levels in the lung tissue of the mice were detected.Beas-2B cells stimulated with lipopolysaccharide(LPS;1 μg/mL)were treated with 2.5,5,or 10 μmol/L curcumin or with 10 μmol/L curcumin combined with 5 μmol/L PX-12,and the changes in MDA,Fe2+and ROS levels were assessed.Western blotting was performed to detect the protein expressions of TXNIP,TRX-1,GPX4 and X-CT in both the mouse lung tissues and Beas-2B cells.Results The mice with CLP-induced sepsis showed severe lung injury with elevated expressions of IL-6,IL-1β,TNF-α,MDA and MPO and decreased GSH expression.In Beas-2B cells,LPS stimulation significantly increased MDA and Fe2+levels and ROS release,increased TXNIP protein expression,and lowered the protein expression levels of TRX-1,GPX4 and X-CT,and these changes were also observed in the septic mice.Curcumin treatments at different concentrations obviously alleviated lung injury in the septic mice and reduced LPS-induced injury in Beas-2B cells.Curcumin significantly decreased the release of inflammatory factors,MDA and MPO,increased GSH level,lowered Fe2+,MDA and ROS levels,increased TXNIP protein expression,and lowered the protein expressions of TRX-1,GPX4 and X-CT in both septic mouse lung tissues and LPS-stimulated Beas-2B cells.The protective effect of curcumin was effectively blocked by PX-12 treatment.Conclusion Curcumin inhibits ferroptosis and alleviates septic lung injury in mice by elevating TRX-1 and GPX4 and decreasing TXNIP in the lung tissue.

Objective To analyze the development trajectory and predictors of endocrine therapy associated arthralgia in breast cancer patients.Methods From January 2022 to July 2022,breast cancer patients in the breast medicine department or outpatients of a tertiary cancer hospital in Hunan Province were selected as respondents using a convenience sampling method.A baseline survey was conducted using the General Information Questionnaire,the Symptom Assessment Scale for Patients Treated with Endocrine Therapy for Breast Cancer,and the Self-Rating Anxiety Scale within 1 week prior to patient treatment.The Symptom Assessment Scale for Patients Treated with Endocrine Therapy for Breast Cancer was used to assess patients'arthralgia levels at 3,6,and 9 months after treatment,and data were analyzed using growth mixed model,univariate analysis of variance,and multiple logistic regression.Results A total of 418 breast cancer patients completed the follow-up,with 235 cases(56.22%)developing arthralgia.3 potential categories of arthralgia develop-ment trajectories were identified:high level-slowly increasing group(11.48%),low level-slowly increasing group(44.74%),and asymptomatic group(43.78%).The results of multifactorial analysis showed that anxiety,history of bone and joint disease,sleep duration,place of residence,monthly household income,and frequency of exercise were predictors of potential categories for the development of trajectory of arthralgia levels associated with endocrine therapy in breast cancer patients(P<0.05).Conclusion Arthralgia levels associated with endocrine therapy in breast cancer patients exhibit different trajec-tories,and clinical staff should emphasize the assessment and intervention of pain levels in patients with the anxiety,a history of bone and joint disease,poor sleep,poor finances,living in urban areas,and low frequency of exercise.

Objective To investigate whether curcumin alleviates septic lung injury by inhibiting ferroptosis through modulating the TXNIP/TRX-1/GPX4 pathway.Methods Male C57BL/6 mice were randomly divided into Sham group,cecal ligation puncture(CLP)-induced sepsis group,CLP with curcumin treatment(50,100,and 200 mg/kg)groups,and CLP with both curcumin(200 mg/kg)and TRX-1 inhibitor PX-12(25 mg/kg)treatment group.Inflammatory factors,MDA,MPO,and GSH levels in the lung tissue of the mice were detected.Beas-2B cells stimulated with lipopolysaccharide(LPS;1 μg/mL)were treated with 2.5,5,or 10 μmol/L curcumin or with 10 μmol/L curcumin combined with 5 μmol/L PX-12,and the changes in MDA,Fe2+and ROS levels were assessed.Western blotting was performed to detect the protein expressions of TXNIP,TRX-1,GPX4 and X-CT in both the mouse lung tissues and Beas-2B cells.Results The mice with CLP-induced sepsis showed severe lung injury with elevated expressions of IL-6,IL-1β,TNF-α,MDA and MPO and decreased GSH expression.In Beas-2B cells,LPS stimulation significantly increased MDA and Fe2+levels and ROS release,increased TXNIP protein expression,and lowered the protein expression levels of TRX-1,GPX4 and X-CT,and these changes were also observed in the septic mice.Curcumin treatments at different concentrations obviously alleviated lung injury in the septic mice and reduced LPS-induced injury in Beas-2B cells.Curcumin significantly decreased the release of inflammatory factors,MDA and MPO,increased GSH level,lowered Fe2+,MDA and ROS levels,increased TXNIP protein expression,and lowered the protein expressions of TRX-1,GPX4 and X-CT in both septic mouse lung tissues and LPS-stimulated Beas-2B cells.The protective effect of curcumin was effectively blocked by PX-12 treatment.Conclusion Curcumin inhibits ferroptosis and alleviates septic lung injury in mice by elevating TRX-1 and GPX4 and decreasing TXNIP in the lung tissue.