The aryl hydrocarbon receptor (AhR) plays a crucial role in regulating many physiological processes. Activating the AhR-CYP1A1 axis has emerged as a novel therapeutic strategy against various inflammatory diseases. Here, a practical in situ cell-based fluorometric assay was constructed to screen AhR-CYP1A1 axis modulators, via functional sensing of CYP1A1 activities in live cells. Firstly, a cell-permeable, isoform-specific enzyme-activable fluorogenic substrate for CYP1A1 was rationally constructed for in-situ visualizing the dynamic changes of CYP1A1 function in living systems, which was subsequently used for discovering the efficacious modulators of the AhR-CYP1A1 axis. Following screening of a compound library, LAC-7 was identified as an efficacious activator of the AhR-CYP1A1 axis, which dose-dependently up-regulated the expression levels of both CYP1A1 and AhR in multiple cell lines. LAC-7 also suppressed macrophage M1 polarization and reduced the levels of inflammatory factors in LPS-induced bone marrow-derived macrophages. Animal tests showed that LAC-7 could significantly mitigate DSS-induced ulcerative colitis and LPS-induced acute lung injury in mice, and markedly reduced the levels of multiple inflammatory factors. Collectively, an optimized fluorometric cell-based assay was devised for in situ functional imaging of CYP1A1 activities in living systems, which strongly facilitated the discovery of efficacious modulators of the AhR-CYP1A1 axis as novel anti-inflammatory agents.

Objective:To investigate the association between serum uric acid trajectories and the risk of renal function decline and diabetic kidney disease(DKD) incidence in elderly patients with type 2 diabetes mellitus.Methods:This retrospective cohort study included 5 037 elderly patients with type 2 diabetes mellitus aged 60 years and above who underwent at least three health examinations between 2019 and 2023, with 2019 as the baseline. Latent growth mixture modeling(LGMM) was employed to identify distinct serum uric acid trajectories. Renal function changes and DKD incidence were followed from 2020 to 2023. Binary logistic regression models were used to assess the association between serum uric acid trajectories and the risks of renal function decline and DKD.Results:Two distinct serum uric acid trajectory groups were identified based on model selection criteria: A stable group( n=4 485, 89.04%) and an inverted U-shaped group( n=552, 10.96%). After adjusting for potential confounders, compared with the stable trajectory group, the inverted U-shaped group showed a significantly increased risk of estimated glomerular filtration rate(eGFR) <60 mL·min -1·(1.73 m 2) -1, ≥25% decline in eGFR, doubling of serum creatinine, and DKD events, with OR(95% CI) of 1.99(1.28-3.09), 2.27(1.65-3.13), 1.52(1.09-3.02), and 1.52(1.27-1.82), respectively(all P<0.05). In addition, multivariate analysis indicated that elevated baseline serum uric acid levels were also associated with an increased risk of adverse renal outcomes and DKD incidence; However, the magnitude of the associations was lower than that observed for serum uric acid trajectory groups. Conclusions:An inverted U-shaped serum uric acid trajectory is significantly associated with an increased risk of renal function progression and DKD in elderly patients with type 2 diabetes mellitus. These findings highlight the importance of long-term dynamic monitoring of serum uric acid levels to facilitate early identification and intervention for high-risk individuals.

Objective·To preliminarily investigate the value of high-order functional magnetic resonance imaging in the evaluation of benign and malignant bone and soft tissue tumors and the changes after chemotherapy.Methods·Patients clinically diagnosed with bone and soft tissue tumors at the Department of Orthopaedics,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,from October 2014 to December 2024 were enrolled.The patients were divided into a control group and an amide proton transfer-weighted imaging(APTw)group according to the imaging method.All patients underwent conventional magnetic resonance imaging(MRI),diffusion-weighted imaging(DWI),and dynamic contrast-enhanced imaging(DCE)before surgery.Patients in the APTw group received additional APTw imaging.Both groups were divided into non-malignant and malignant lesion subgroups according to pathological results.According to whether the patients received chemotherapy before enrollment,the patients with malignant lesions in the APTw group were further divided into malignant group without chemotherapy and malignant group with chemotherapy.Clinical and imaging data,including APT values,apparent diffusion coefficient(ADC),and time-intensity curves(TICs)from the largest tumor section,were collected and analyzed to assess the diagnostic performance of APTw,DWI,and DCE,and to evaluate changes after chemotherapy.Results·Eighty-five patients were enrolled,including 51 males and 34 females,with ages ranging from 10 to 84 years,and a mean age of(43.05±17.62)years.There were 51 patients in the control group(16 with non-malignant lesions and 35 with malignant lesions)and 34 patients in the APTw group(5 with non-malignant lesions and 29 with malignant lesions;23 malignant lesions without chemotherapy and 6 malignant lesions with chemotherapy).The clinical and imaging data showed that only the tumor margin of the control group and the maximum tumor diameter of the APTw group had statistically significant differences in their malignant and non-malignant lesion groups(P<0.05).In the APTw group,there was a statistically significant difference in APT values between the malignant lesion group and the non-malignant lesion group(P<0.001).Further analysis showed that the APT values in the malignant group without chemotherapy were significantly lower than that in the malignant group with chemotherapy(P<0.001).However,there were no statistically significant differences in APT values between the malignant group with chemotherapy and the non-malignant lesion group(P>0.05).There were no significant differences in ADC values and TIC types between malignant and non-malignant lesion groups in the control group and the APTw group(P>0.05).The area under the curve(AUC)of the diagnostic model in the APTw group(MRI+DWI+DCE+APTw)for distinguishing malignant from benign tumors was significantly higher than that of the control group(MRI+DWI+DCE)(P<0.05).The Youden index and specificity of the diagnostic model in the APTw group were higher than those in the control group.Conclusion·As a high-order functional MRI technique,APTw imaging is capable of evaluating the nature(benign or malignant)of bone and soft tissue tumors and detecting changes after chemotherapy.It serves as a valuable supplement to conventional MRI,DWI,and DCE imaging,providing a novel noninvasive tool for the diagnosis and treatment evaluation of bone and soft tissue tumors.

Objective·To preliminarily investigate the value of high-order functional magnetic resonance imaging in the evaluation of benign and malignant bone and soft tissue tumors and the changes after chemotherapy.Methods·Patients clinically diagnosed with bone and soft tissue tumors at the Department of Orthopaedics,Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine,from October 2014 to December 2024 were enrolled.The patients were divided into a control group and an amide proton transfer-weighted imaging(APTw)group according to the imaging method.All patients underwent conventional magnetic resonance imaging(MRI),diffusion-weighted imaging(DWI),and dynamic contrast-enhanced imaging(DCE)before surgery.Patients in the APTw group received additional APTw imaging.Both groups were divided into non-malignant and malignant lesion subgroups according to pathological results.According to whether the patients received chemotherapy before enrollment,the patients with malignant lesions in the APTw group were further divided into malignant group without chemotherapy and malignant group with chemotherapy.Clinical and imaging data,including APT values,apparent diffusion coefficient(ADC),and time-intensity curves(TICs)from the largest tumor section,were collected and analyzed to assess the diagnostic performance of APTw,DWI,and DCE,and to evaluate changes after chemotherapy.Results·Eighty-five patients were enrolled,including 51 males and 34 females,with ages ranging from 10 to 84 years,and a mean age of(43.05±17.62)years.There were 51 patients in the control group(16 with non-malignant lesions and 35 with malignant lesions)and 34 patients in the APTw group(5 with non-malignant lesions and 29 with malignant lesions;23 malignant lesions without chemotherapy and 6 malignant lesions with chemotherapy).The clinical and imaging data showed that only the tumor margin of the control group and the maximum tumor diameter of the APTw group had statistically significant differences in their malignant and non-malignant lesion groups(P<0.05).In the APTw group,there was a statistically significant difference in APT values between the malignant lesion group and the non-malignant lesion group(P<0.001).Further analysis showed that the APT values in the malignant group without chemotherapy were significantly lower than that in the malignant group with chemotherapy(P<0.001).However,there were no statistically significant differences in APT values between the malignant group with chemotherapy and the non-malignant lesion group(P>0.05).There were no significant differences in ADC values and TIC types between malignant and non-malignant lesion groups in the control group and the APTw group(P>0.05).The area under the curve(AUC)of the diagnostic model in the APTw group(MRI+DWI+DCE+APTw)for distinguishing malignant from benign tumors was significantly higher than that of the control group(MRI+DWI+DCE)(P<0.05).The Youden index and specificity of the diagnostic model in the APTw group were higher than those in the control group.Conclusion·As a high-order functional MRI technique,APTw imaging is capable of evaluating the nature(benign or malignant)of bone and soft tissue tumors and detecting changes after chemotherapy.It serves as a valuable supplement to conventional MRI,DWI,and DCE imaging,providing a novel noninvasive tool for the diagnosis and treatment evaluation of bone and soft tissue tumors.

Objective:To investigate the association between serum uric acid trajectories and the risk of renal function decline and diabetic kidney disease(DKD) incidence in elderly patients with type 2 diabetes mellitus.Methods:This retrospective cohort study included 5 037 elderly patients with type 2 diabetes mellitus aged 60 years and above who underwent at least three health examinations between 2019 and 2023, with 2019 as the baseline. Latent growth mixture modeling(LGMM) was employed to identify distinct serum uric acid trajectories. Renal function changes and DKD incidence were followed from 2020 to 2023. Binary logistic regression models were used to assess the association between serum uric acid trajectories and the risks of renal function decline and DKD.Results:Two distinct serum uric acid trajectory groups were identified based on model selection criteria: A stable group( n=4 485, 89.04%) and an inverted U-shaped group( n=552, 10.96%). After adjusting for potential confounders, compared with the stable trajectory group, the inverted U-shaped group showed a significantly increased risk of estimated glomerular filtration rate(eGFR) <60 mL·min -1·(1.73 m 2) -1, ≥25% decline in eGFR, doubling of serum creatinine, and DKD events, with OR(95% CI) of 1.99(1.28-3.09), 2.27(1.65-3.13), 1.52(1.09-3.02), and 1.52(1.27-1.82), respectively(all P<0.05). In addition, multivariate analysis indicated that elevated baseline serum uric acid levels were also associated with an increased risk of adverse renal outcomes and DKD incidence; However, the magnitude of the associations was lower than that observed for serum uric acid trajectory groups. Conclusions:An inverted U-shaped serum uric acid trajectory is significantly associated with an increased risk of renal function progression and DKD in elderly patients with type 2 diabetes mellitus. These findings highlight the importance of long-term dynamic monitoring of serum uric acid levels to facilitate early identification and intervention for high-risk individuals.

Sepsis-induced lung injury is a common type of sepsis complicated with multiple organ dysfunction syndrome,whose uncontrolled inflammatory response and oxidative stress are the key pathological mechanisms.As an important pathway of anti-inflammatory and anti-oxidative stress,the nuclear factor-erythroid 2-related factor 2(Nrf2)signaling pathway is very important in the occurrence and development of sepsis-induced lung injury.This review summarizes relevant research conducted over the past decade on the regulation of the Nrf2 signaling pathway by traditional Chinese medicine(TCM)to ameliorate sepsis-induced lung injury.It has been found that 14 kinds of TCM effective ingredients(including five types of compounds:flavonoids,terpenes,alkaloids,saponins,phenols)and 6 kinds of compound preparations(including three types of formulas:heat-clearing and detoxifying formulas,purgative formulas for promoting bowel movement,and formulas for reinforcing vital qi and consolidating the constitution)can inhibit inflammatory responses and oxidative stress by activating Nrf2 signaling pathway and intervening in related pathways such as those involving Kelch-like ECH-associated protein 1,heme oxygenase-1,antioxidant response element and AMP-activated protein kinase,thereby alleviating sepsis-induced lung injury.

Objective To quantitatively analyze the effects of population aging and other risk factors on the burden of colorectal cancer in China from 1990 to 2019. Methods The Global Burden of Disease Study 2019 was used to describe the temporal trend of the burden of colorectal cancer. A decomposition method established by Gupta was applied to quantify the burden related to population growth, aging, age-specific prevalence, and disease severity. Results The age-standardized disability adjusted life years (DALY) rates of colorectal cancer in China showed an overall upward trend from 1990 to 2019. The DALY in 2019 increased by 191.12% compared with that in 1990, with 34.54% of the increase attributed to population growth, 111.36% to population aging, and 77.56% to the rise of age-specific prevalence. Meanwhile, -32.54% benefited from the changes in disease severity. Diet low in milk was the primary risk factor for the disease burden of colorectal cancer in China in 2019, followed by diet low in whole grains and calcium. In the last 30 years, the corresponding risk factor of the most rapid increase in China was high BMI with an average annual percentage of change of 4.14%, and the corresponding risk factor of the most rapid decrease in China was diet low in fiber with an average annual percentage of change of -2.00%. Conclusion Aging population is mainly responsible for the considerable increase in the burden of colorectal cancer in China from 1990 to 2019. The health administrative authorities should take corresponding measures to address the adverse impacts associated with aging.

Objective:To understand the epidemiological characteristics and trends of injury in older adults in Jiangsu Province from 2006 to 2022 and provide a scientific basis for developing prevention and control measures.Methods:The data on injury cases aged 60 and older were collected from 12 sentinel hospitals in Jiangsu Province during 2006-2022. The study analyzed the proportion of injury cases among the elderly in the overall population and calculated the annual percent change and average annual percent change (AAPC). A pairwise comparison between groups was performed, and the differences were judged according to the adjusted standardized residuals.Results:From 2006 to 2022, there were 218 426 injury cases among individuals aged 60 and older in Jiangsu Province, which accounted for an increasing proportion of injury cases within the entire population (AAPC=3.17%, P<0.001). The first five causes of elderly injury were falls (42.06%), road traffic injuries (20.20%), animal injuries (11.45%), knife/sharp injuries (9.43%), and blunt injuries (8.13%). From 2006 to 2022, the proportion of falls, animal injuries, and knife/sharp injuries among the elderly aged ≥60 showed an increasing trend, while the proportion of road traffic injuries and blunt injuries decreased (all P<0.001). The incidence of injury was highest in October, with a daily incidence peak between 8:00 and 10:00. Leisure activities (40.34%) were the major activity leading to injury. The injury occurred mainly at home (53.74%), and the injury intention was mainly unintentional (97.41%), all of which showed an increasing trend ( P<0.001). The injuries were mainly bruises (36.00%), and the most common injured positions of the body were low limbs (27.55%), all of which showed a decreasing trend ( P<0.001). About 69.80% of cases were slight, and 79.38% were discharged after treatment, which showed an increasing trend ( P<0.001). Conclusions:The injury data for individuals aged 60 and older in Jiangsu Province exhibited varying trends from 2006 to 2022. There was a noticeable increase in the proportion of elderly injury cases within the overall injury population, as well as an upward trend in falls, animal injuries, and knife/sharp injuries as leading causes of injury. It is imperative to actively develop prevention measures based on the epidemiological characteristics and evolving trends of elderly injuries in Jiangsu Province.

Objective:To construct an "Internet + transitional care" scheme for patients with atrial fibrillation after radiofrequency ablation based on ABC overall pathway management, so as to provide reference for the transitional care of patients with atrial fibrillation after surgery.Methods:Through literature review, the first draft of "Internet + transitional care" scheme for patients with atrial fibrillation after radiofrequency ablation based on ABC overall path management was developed. The convenient sampling method was adopted, 16 experts were selected for two rounds of Delphi expert letter consultations and program items were adjusted. Finally, the final draft of "Internet + transitional care" scheme for patients with atrial fibrillation after radiofrequency ablation based on ABC overall pathway management was formed.Results:The effective recovery rates of the two rounds of expert letter consultation were 100.00% (16/16) and 93.75% (15/16) , and the authority coefficients were 0.87 and 0.88, respectively. The Kendall's concordance coefficients of the two rounds of expert consultation were statistically significant ( P<0.05 ) . Finally, a scheme of 70 items was formed, including the day of discharge, 1 week after surgery and 1, 3 and 6 months after surgery. Conclusions:The scheme constructed in this study is scientific and operable and comprehensively reflects the comprehensive management strategy from three aspects, which is worthy of clinical application.