OBJECTIVE To evaluate the cost-effectiveness of finerenone combined with standard treatment regimen in the treatment of diabetic nephropathy （DN）. METHODS From the perspective of healthcare service providers， a Markov model was established to simulate the dynamic changes of each stage in DN patients who received finerenone combined with the standard treatment regimen or the standard treatment regimen alone based on the phase Ⅲ clinical trial study of finerenone for DN. Markov model was used to perform the cost-effectiveness of long-term effects and the costs of the two therapies with a simulation cycle of 4 months， a simulation period of 15 years and an annual discount rate of 5%. At the same time， one-way sensitivity analysis and probability sensitivity analysis were performed， and the stability of the results was validated. RESULTS Accumulative cost of the standard treatment regimen was 579 329.54 yuan， and the accumulative utility was 8.052 4 quality-adjusted life year （QALYs）； the accumulative cost of finerenone combined with the standard treatment regimen was 332 520.61 yuan， and the accumulative utility was 8.187 4 QALYs. Finerenone combined with the standard treatment regimen was more cost-effective. The results of one-way sensitivity analysis showed that dialysis status utility value， DN stage 3 utility value and DN stage 4 utility value had a great influence on the incremental cost-effectiveness ratio， but did not affect the robustness of the model. The results of probability sensitivity analysis showed that finerenone combined with the standard treatment regimen was more cost-effective with 100% probability. CONCLUSIONS For DN patients， finerenone combined with the standard treatment regimen is more cost-effective as an absolute advantage option.

With the rapid development of sequencing technologies, the detection of alternative polyadenylation (APA) in mammals has become more precise. APA precisely regulates gene expression by altering the length and position of the poly(A) tail, and is involved in various biological processes such as disease occurrence and embryonic development. The research on APA in mammals mainly focuses on the following aspects:(1) identifying APA based on transcriptome data and elucidating their characteristics; (2) investigating the relationship between APA and gene expression regulation to reveal its important role in life regulation;(3) exploring the intrinsic connections between APA and disease occurrence, embryonic development, differentiation, and other life processes to provide new perspectives and methods for disease diagnosis and treatment, as well as uncovering embryonic development regulatory mechanisms. In this review, the classification, mechanisms and functions of APA were elaborated in detail and the methods for APA identifying and APA data resources based on various transcriptome data were systematically summarized. Moreover, we epitomized and provided an outlook on research on APA, emphasizing the role of sequencing technologies in driving studies on APA in mammals. In the future, with the further development of sequencing technology, the regulatory mechanisms of APA in mammals will become clearer.

Objective To analyze the disease burden of chronic kidney diseases (CKD) attributed to high body mass index (BMI) in China from 1992 to 2021 and predict the disease burden for the next decade, and to provide evidence for the prevention and treatment of CKD. Methods Using the Global Burden of Disease (GBD) database and the Joinpoint model, the average annual percentage rate change (AAPC) of the mortality rate and disability-adjusted life year (DALY) rate was calculated to describe and analyze the CKD disease burden attributed to high BMI in China from 1992 to 2021. The ARIMA model was employed to predict and analyze the change trend of the CKD disease burden. Results From 1992 to 2021, the mortality rate and DALY rate attributed to high BMI-induced chronic kidney disease showed an upward trend. Compared to 1992, the attributed number of deaths increased by 324.38%, and DALYs increased by 268.56%; the mortality rate increased by 64.00%, and the DALY rate grew by 51.62%. From 1992 to 2021, the mortality rate and DALY rate for males were lower than those for females, but the growth rate for males exceeded that of females. From 1992 to 2021, the mortality rate and DALY rate of chronic kidney disease attributed to high BMI in China increased with age. The average annual change rate of chronic kidney disease attributed to high BMI in China from 1992 to 2021 (mortality rate: 1.40 per 100,000 (95% CI: 1.04–1.76), DALY rate: 1.43 per 100 000 (95% CI: 1.17–1.70)) was higher than thHuaiyin Normal University, Huai'anher social demographic index (SDI) regions. The ARIMA model predicted that the age-standardized mortality rate increased from 2.91 per 100 000 in 2022 to 3.05 per 100 000 in 2026, and the age-standardized DALY rate increased from 69.65 per 100 000 in 2022 to 73.58 per 100 000 in 2026. Conclusion Chronic kidney disease attributed to high BMI in China is on the rise, and it will continue to grow in the future. The focus of CKD prevention and control should be on males and the elderly, while active measures should be taken to reduce the occurrence and progression of chronic kidney disease.

ObjectiveTo investigate the influence of histone deacetylase 3 (HDAC3) on the occurrence, development of psoriasis-like inflammation in mice, and the relative immune mechanisms. MethodsHealthy C57BL/6 mice aged 6-8 weeks were selected and randomly divided into 3 groups: control group (Control), psoriasis model group (IMQ), and HDAC3 inhibitor RGFP966-treated psoriasis model group (IMQ+RGFP966). One day prior to the experiment, the back hair of the mice was shaved. After a one-day stabilization period, the mice in Control group was treated with an equal amount of vaseline, while the mice in IMQ group was treated with imiquimod (62.5 mg/d) applied topically on the back to establish a psoriasis-like inflammation model. The mice in IMQ+RGFP966 group received intervention with a high dose of the HDAC3-selective inhibitor RGFP966 (30 mg/kg) based on the psoriasis-like model. All groups were treated continuously for 5 d, during which psoriasis-like inflammation symptoms (scaling, erythema, skin thickness), body weight, and mental status were observed and recorded, with photographs taken for documentation. After euthanasia, hematoxylin-eosin (HE) staining was used to assess the effect of RGFP966 on the skin tissue structure of the mice, and skin thickness was measured. The mRNA and protein expression levels of HDAC3 in skin tissues were detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot (WB), respectively. Flow cytometry was employed to analyze neutrophils in peripheral blood and lymph nodes, CD4⁺ T lymphocytes, CD8⁺ T lymphocytes in peripheral blood, and IL-17A secretion by peripheral blood CD4⁺ T lymphocytes. Additionally, spleen CD4⁺ T lymphocyte expression of HDAC3, CCR6, CCR8, and IL-17A secretion levels were analyzed. Immunohistochemistry was used to detect the localization and expression levels of HDAC3, IL-17A, and IL-10 in skin tissues. ResultsCompared with the Control group, the IMQ group exhibited significant psoriasis-like inflammation, characterized by erythema, scaling, and skin wrinkling. Compared with the IMQ group, RGFP966 exacerbated psoriasis-like inflammatory symptoms, leading to increased hyperkeratosis. The psoriasis area and severity index (PASI) skin symptom scores were higher in the IMQ group than those in the Control group, and the scores were further elevated in the IMQ+RGFP966 group compared to the IMQ group. Skin thickness measurements showed a trend of IMQ+RGFP966>IMQ>Control. The numbers of neutrophils in the blood and lymph nodes increased sequentially in the Control, IMQ, and IMQ+RGFP966 groups, with a similar trend observed for CD4⁺ and CD8⁺ T lymphocytes in the blood. In skin tissues, compared with the Control group, the mRNA and protein levels of HDAC3 decreased in the IMQ group, but RGFP966 did not further reduce these expressions. HDAC3 was primarily located in the nucleus. Compared with the Control group, the nuclear HDAC3 content decreased in the skin tissues of the IMQ group, and RGFP966 further reduced nuclear HDAC3. Compared with the Control and IMQ groups, RGFP966 treatment decreased HDAC3 expression in splenic CD4⁺ and CD8⁺ T cells. RGFP966 treatment increased the expression of CCR6 and CCR8 in splenic CD4⁺ T cells and enhanced IL-17A secretion by peripheral blood and splenic CD4⁺ T lymphocytes. Additionally, compared with the IMQ group, RGFP966 reduced IL-10 protein levels and upregulated IL-17A expression in skin tissues. ConclusionRGFP966 exacerbates psoriatic-like inflammatory responses by inhibiting HDAC3, increasing the secretion of the cytokine IL-17A, and upregulating the expression of chemokines CCR8 and CCR6.

A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Objective: To investigate treatment strategies for chronic periapical periodontitis in prematurely erupted premolars and provide guidance for managing pulp and periapical diseases in young permanent teeth with immature roots. Methods: A regenerative endodontic procedure (REP) was performed on a prematurely erupted maxillary left first premolar (tooth 24) at Nolla stage Ⅶ with chronic apical periodontitis, following standardized protocols including root canal irrigation, disinfection, and coronal sealing. The case was followed up, and a literature review was conducted. Results: Clinical resolution of symptoms was observed on tooth 24, with sustained root development. After a 20-month follow-up, the tooth had restored biological function. Literature synthesis revealed that periapical infections in prematurely erupted permanent teeth predominently arise from pulp exposure and bacterial infection, with retrograde infection being rare. For young permanent teeth with necrotic pulp, regenerative endodontic procedures has been established as the treatment of choice to promote apical closure and root maturation. The critical steps of regenerative endodontic procedures include thorough disinfection, induced bleeding to form a fibrin scaffold, and coronal sealing to facilitate stem cell recruitment and differentiation. Conclusion Regenerative endodontic procedures represents an effective and viable treatment option for prematurely erupted young permanent teeth with chronic periapical periodontitis.

Objective: To explore the independent effects and gender differences of different types of adverse childhood experiences (ACEs) on the co-occurrence of non-suicidal self-injury (NSSI) and suicide attempts (SA), so as to provide a reference for the precise prevention and control of self-harm in junior high school students. Methods: From May to June 2023, a total of 7 360 junior high school students were selected from 12 schools in three districts/counties of Chongqing using a combination of stratified cluster sampling and convenience sampling methods. Information on NSSI, SA, ACEs, and depressive symptom, as well as other related data were collected through the Adolescent Non-suicidal Self-injury Assessment Questionnaire (ANSAQ), suicide related section of the Chinese Adolescent Health related Behavior Questionnaire (Junior High School Version), Childhood Trauma Questionnaire-Short Form ( CTQ- SF), and Center for Epidemiologic Studies-Depression Scale (CES-D). Statistical analyses of the data were performed using the Chi-square test and multiple Logistic regression. Results: The detection rates of NSSI, SA, NSSI+SA and ACEs in junior high school students were 19.2%, 4.6%, 3.5% and 57.9% respectively. After controlling for factors such as gender, grade, family type, self rated family economic status, self rated academic performance, self rated academic pressure, number of close friends, and depressive symptom scores, results from the multiple Logistic regression analysis showed that junior high school students with physical abuse ( OR = 1.98, 95% CI =1.23-3.18), emotional abuse ( OR =2.83, 95% CI =1.92-4.19), sexual abuse ( OR = 1.70, 95% CI =1.07- 2.69 ), physical neglect ( OR =1.67, 95% CI =1.20-2.33) and witnessing domestic violence ( OR =2.10, 95% CI =1.41-2.87) in childhood had higher risks for the occurrence of NSSI+SA (all P <0.05). After stratification by gender, boys with sexual abuse in childhood had a high risk for the occurrence of NSSI+SA ( OR =2.17, 95% CI =1.06-4.43), whereas girls with emotional abuse ( OR =3.69, 95% CI =2.29-5.94), physical neglect ( OR =1.62, 95% CI =1.07-2.45) and witnessing domestic violence ( OR =2.17, 95% CI =1.41-3.34) in childhood had hgih risks for the occurrence of NSSI+SA (all P <0.05). Conclusions Different types of ACEs have different effects on the co-occurrence of self-harm in junior high school students and there are gender differences. When family interventions are conducted for the combined model, emphasis should be placed on aspects of emotional abuse and domestic violence while optimizing the interventions based on gender differences.

Objective: To understand the current situation and influencing factors of comorbidity of depressive and anxiety symptoms among middle school students in Chongqing, so as to provide a scientific basis for formulating a comprehensive strategy for the co prevention of multiple diseases among middle school students. Methods: From September to December 2024, 12 327 middle school students were selected from 6 districts and counties in Chongqing by the combination of stratified cluster sampling and convenience sampling method. The current status of depressive and anxiety symptoms was investigated by using the Center for Epidemiological Survey-Depression Scale (CES-D) and the Generalized Anxiety Disorder-7 (GAD-7). The Chi-squared test was used to compare the differences between groups with comorbidity of depressive and anxiety symptoms, multivariate Logistic regression analysis was used to analyze its related factors, and a nomogram prediction model was drawn. Results: The detection rates of depressive symptoms, anxiety symptoms and comorbidity among middle school students in Chongqing were 26.34%, 34.55% and 21.16%, respectively. Among them, the detection rates of the three types of symptoms in girls (29.80%, 40.99%, 25.15%) were all higher than those in boys (23.22%, 28.73%, 17.55%) ( χ 2=68.61, 204.23, 106.51, all P <0.01). Statistical significance was observed in the distribution of depressive and anxious symptoms among middle school students across different gender, academic stage, school district, family type, physical activity levels, parental discipline, smoking, alcohol consumption, sleep deprivation, excessive screen time, Internet addiction, and bullying ( χ 2=14.49-991.46, all P <0.01). Multivariate Logistic regression analysis showed that compared with junior high school students, ordinary high school students had a higher risk of comorbidity ( OR=2.71, 95% CI = 2.41-3.05); girls ( OR=2.17, 95%CI =1.95-2.40), non-core family ( OR=1.20, 95%CI =1.08-1.32), and good neighborhood ( OR=1.16, 95%CI =1.02-1.30), campus bullying ( OR=4.88, 95%CI =4.32-5.50), Internet addiction ( OR=4.77, 95%CI = 3.41 -6.68), parental beating and scolding ( OR=3.18, 95%CI =2.72-3.71), alcohol consumption ( OR=2.10, 95%CI =1.86- 2.37 ), and insufficient sleep ( OR=1.73, 95%CI =1.54-1.95) had higher risks with comorbidity of depression and anxiety symptoms (all P <0.05). A nomogram prediction model was constructed based on significant variables shows that C-index=0.75 (AUC= 0.75 , 95% CI=0.74-0.76, P <0.05), and the model had good predictive performance. Conclusions The current situation of comorbidity of depressive and anxiety symptoms among middle school students in Chongqing is not optimistic. The nomograms can be used to effectively predict the risk of comorbidity of depressive and anxiety symptoms in middle school students.

Background Deoxynivalenol (DON), a priority contaminant for food safety risk monitoring, is produced by Fusarium spp. infesting crops, and its common derivatives are 3-acetyl-DON (3A-DON) and 15-acetyl-DON (15A-DON), which have been shown to possess gastrointestinal toxicity, immunotoxicity, reproductive toxicity, and cytotoxicity. Due to the stable physicochemical properties of the DON family of toxins (DONs), they cannot be effectively removed during food processing, thus following the food chain, entering the human body, and posing health risks. Objective To understand the contamination status of DONs in commercial foods (cereals and bakery products) in Shanghai in 2022–2023, and to assess the exposure risk of DONs in pregnant women by combining their dietary consumption data. Methods Liquid chromatography tandem mass spectrometry (LC-MS/MS) was used to determine the contamination level of DONs in 1 100 food samples (cereals and baked goods) collected in 2022 and 944 samples collected in 2023 from Shanghai. The dietary monitoring data of pregnant women in Shanghai from 2016 to 2017 were adopted. The monitoring employed the food frequency questionnaire distributed among pregnant women through a combination of online telephone enquiry and offline on-site face-to-face survey to estimate their food consumption levels. An exposure assessment model was established to calculate the exposure level to DONs, and the probability distribution of the DONs exposure level in the pregnant women group in Shanghai was obtained by applying @Risk 7.5 software and simulating the calculation according to the Monte Carlo principle. With reference to the tolerable daily intake (TDI) of DONs [1.00 µg·(kg·d)⁻¹] proposed by the Joint FAO/WHO Expert Committee on Food Additives, the risk of exposure to DONs from commercial cereals and bakery products in pregnant women in Shanghai was assessed. Results DONs were detected in cereal and bakery samples collected in 2022 and 2023 with different levels of contamination. The level of DONs in cereal foods in 2023 (mean: 36.33 µg·kg⁻¹) decreased compared to 2022 (mean: 23.64 µg·kg⁻¹). However, the positive rate (71.67%) and level (mean: 51.22 µg·kg⁻¹) of DONs in bakery products increased significantly compared with 2022 (positive rate: 10.00%, mean: 24.39 µg·kg⁻¹). The mean consumption of cereals in 783 pregnant women was 222.48 g·d⁻¹ and the mean consumption of bakery products was 36.07 g·d⁻¹, and there was no statistically significant difference in the intake of all types of cereals and bakery products across the early, middle, and late stages of pregnancy. The modelled intakes of DONs via commercial cereals and bakery products for pregnant women in Shanghai were calculated to be 0.20 and 0.57 µg·(kg·d)⁻¹ in 2022 for the mean level and the 95th percentile level, respectively, and 0.16 µg·(kg·d)⁻¹ and 0.35 µg·(kg·d)⁻¹ in 2023, respectively. The results of the health risk assessment showed that pregnant women in Shanghai had 2.6% and 1.4% probability of exposure to DONs from cereal consumption in 2022 and 2023, respectively. Conclusion The risk of exposure of pregnant women in Shanghai to DONs via commercial cereals and bakery products is relatively low (1.4%-2.6%). However, considering the physical sensitivity of pregnant women, they should avoid consuming moldy grains and appropriately reduce intake of bakery products.

Objective To study the role of sphingosine-1-phosphate(S1P)signal on the proliferation of breast cancer BT549 cells.Methods Cells were divided into control group and experimental group,experimental group were treated with 0.1,1.0,10.0 μmol·L-1 S1P receptor agonist SEW2871 for 72 h.Control group was cultured with 0.1％fetal bovine serum.Cell proliferation was detected by methyl thiazolyl tetrazolium(MTT)assay.Cell models of overexpressing S1P receptors in BT549 were divided into three groups:blank plasmid group(LUC),wild type S1P receptor overexpression group(WT),S1P receptor phosphorylation site mutation overexpression group(MUT);the proliferation ratio was detected by MTT,the number of cell clones was counted by colony formation experiment.S1P antagonist W146(10 μmol·L-1)and protein kinase(AKT)signaling inhibitor MK2206(90 nmol·L-1)were used to detect the role of S1P signaling in the proliferation of breast cancer cells.The expression of phosphorylate signal transducer and activator of transcription 3(p-STAT3),c-Myc proteins were detected by Western blot.Results The growth ratio of BT549 cells in control group and 0.1,1.0,10.0 μmol·L-1experimental groups were 1.00±0.03,1.13±0.06,1.06±0.10 and 1.07±0.03,0.1 μmol·L-1 SEW2871 promot the cell proliferation(P＜0.05).Compared between WT group,MUT group and LUC group,the growth rate and the number of clonal colonies were increased after overexpression of S1P receptor(all P＜0.05).The growth ratio of BT549 cells after treatment with W146 and MK2206 in the LUC group,WT group and MUT group were 1.25±0.12,1.31±0.03,1.43±0.14 and 0.87±0.15,0.77±0.03,0.88±0.02.Compared between MUT group,WT group and corresponding DMSO group,the differences were statistically significant(all P＜0.01).The number of cell clony formation number after treatment with W146 were 65.65±5.12,141.48±5.63 and 93.64±5.14;compared between MUT,WT group and corresponding DMSO group,the differences were statistically significant(all P＜0.05).The relative protein expression levels of p-STAT3 in LUC group,WT group and MUT group were 0.67±0.04,0.69±0.08 and 0.81±0.06,the relative protein expression levels of proto-oncogene c-Myc were 1.69±0.03,0.70±0.10 and 0.67±0.07,compared between WT group,MUT group and corresponding DMSO group,the difference was statistically significant(P＜0.05).Conclusion S1P signaling can promote proliferation in breast cancer BT549 cells,and the mechanism could be related to AKT and STAT3 signaling pathway.