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 independent risk factors for poor prognosis in patients with acute pancreatitis （AP） by analyzing inflammatory factors， lung ultrasound （LUS） scores， and CT scores， to establish a nomogram prediction model， and to provide a basis for early clinical intervention. MethodsA total of 409 patients with AP who were admitted to Changshu Hospital Affiliated to Soochow University from January 2021 to October 2023 were enrolled as subjects， and they were divided into modeling group with 288 patients and validation group with 121 patients using the simple random sampling method at a ratio of 7∶3. According to the prognosis， each group was further divided into poor prognosis group and good prognosis group. The levels of C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and tumor necrosis factor-α （TNF-α） were measured for both groups within 72 hours after admission， and LUS scores， modified CT severity index （MCTSI）， and extrapancreatic inflammation on computed tomography （EPIC） scores were assessed within 48‍ ‍—‍ ‍72 hours after admission. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. A LASSO regression analysis was used to screen for the variables that were included in the multivariate logistic regression model to identify the independent risk factors for the poor prognosis of AP， and then a nomogram prediction model was established. The receiver operating characteristic （ROC） curve and the calibration curve were used to assess the discriminatory ability and goodness of fit of the nomogram model， and a decision curve analysis was used to assess the clinical applicability of the model. ResultsAmong the 288 patients with AP in the modeling group， there were 33 （11.46%） in the poor prognosis group and 255 （88.54%） in the good prognosis group； among the 121 patients with AP in the validation group， there were 13 （10.74%） in the poor prognosis group and 108 （89.26%） in the good prognosis group. Compared with the good prognosis group， the poor prognosis group had significantly higher levels of CRP （Z=3.607， P<0.05）， IL-6 （Z=4.189， P<0.05）， and TNF-α （t=2.584， P<0.05）， and significantly higher scores of LUS （t=8.075， P<0.05）， MCTSI （t=5.929， P<0.05）， and EPIC （t=8.626， P<0.05）. The multivariate logistic regression analysis showed that CRP （odds ratio ［OR］=3.592， 95% confidence interval ［CI］： 1.272‍ ‍—‍ ‍10.138， P<0.05）， IL-6 （OR=4.225， 95%CI： 1.468‍ ‍—‍ ‍12.156， P<0.05）， TNF-α （OR=3.540， 95%CI： 1.205‍ ‍—‍ ‍10.401， P<0.05）， LUS （OR=7.094， 95%CI： 2.398‍ ‍—‍ ‍20.986， P<0.05）， MCTSI （OR=7.612， 95%CI： 2.832‍ ‍—‍ ‍20.462， P<0.05）， and EPIC （OR=11.915， 95%CI： 4.007‍ ‍—‍ ‍35.432， P<0.05） were independent risk factor for poor prognosis in patients with AP. A nomogram prediction model was established based on the above 6 indicators， which had an area under the ROC curve of 0.924 （95%CI： 0.883‍ ‍—‍ ‍0.964）， and the Youden index for the optimal cut-off value was 0.670， with a sensitivity of 0.909 and a specificity of 0.761. The calibration curve showed good consistency between the predicted and observed results in both the modeling group and the validation group. The decision curve analysis showed that the predictive model had certain clinical effectiveness. ConclusionThe nomogram model for predicting the risk of poor prognosis in AP patients based on CRP， IL-6， TNF-α， LUS score， MCTSI score， and EPIC score has relatively good predictive performance and can provide important strategic guidance for developing early intensified treatment regimens for AP patients in clinical practice.

This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

OBJECTIVE: To explore the improvement effect of rehabilitation nursing based on information-knowledge-belief-behavior (IKAP) theory on urinary incontinence patients after radical prostatectomy. METHODS Sixty-six patients with urinary incontinence who received robot-assisted laparoscopic radical prostatectomy in General Hospital of Eastern Theater Command from January 2021 to January 2023 were selected and divided into control group (n=33) and observation group (n=33) according to random number table method. The patients in the control group were treated with rehabilitation nursing. The patients in the observation group were treated with rehabilitation nursing guided by IKAP theory. The recovery of urinary incontinence, duration of urinary incontinence, subjective well-being, quality of life, psychological and emotional indexes of patients in the two groups were compared. Results： The total effective rate of urinary incontinence recovery in the observation group was significantly higher than that in the control group (90.91% vs 60.61%，P<0.05). The duration of urinary incontinence in the observation group was significantly shorter than that in the control group (［3.36±1.54］d vs ［4.15±1.36］d，P<0.05). And the subjective well-being score in observation group was significantly higher than that in the control group (［19.36±2.69］points vs ［11.65±2.65］points， P<0.05). There was no significant difference in preoperative physical function, social function，and mental health scores between the two groups (P>0.05). And all scores in the observation group were significantly higher than those in the control group after surgery (P<0.05). There was no significant difference in the preoperative SAS and SDS scores between the two groups of patients (P>0.05). And the scores of SAS and SDS in observation group were lower than those of the control group after the operation (P<0.05). Conclusion： Rehabilitation nursing based on IKAP theory can significantly improve urinary incontinence in patients with prostate cancer after surgery, which promotes the recovery of urinary incontinence, shortens the time of urinary incontinence, and improves the subjective well-being and quality of life, as well as reduces the negative impact of negative emotions. Therefore, it can be widely promoted and implemented in clinical practice.
Humans ; Prostatectomy/adverse effects* ; Urinary Incontinence/etiology* ; Male ; Quality of Life ; Rehabilitation Nursing ; Middle Aged ; Aged

Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) can enhance the anti-tumor activity of the anti-programmed cell death-1 (anti-PD-1) antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not performed, and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) that can be used to predict the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared with VEGFRi alone, the combination of anti-PD-1 antibody and VEGFRi exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and a similar adverse event incidence. Through single-cell and spatial transcriptomic analysis, we determined ten MSS CRC-enriched immune cell types and their spatial distribution, including naive CD4⁺ T, regulatory CD4⁺ T, CD4⁺ Th17, exhausted CD8⁺ T, cytotoxic CD8⁺ T, proliferated CD8⁺ T, natural killer (NK) cells, plasma, and classical and intermediate monocytes. Based on a systemic meta-analysis and ten machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC patients receiving immunotherapy was also validated with an in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.
Humans ; Colorectal Neoplasms/drug therapy* ; Male ; Female ; Immunotherapy ; Middle Aged ; Aged ; Tumor Microenvironment/immunology* ; Retrospective Studies ; Microsatellite Instability ; Transcriptome ; Single-Cell Analysis ; Programmed Cell Death 1 Receptor/immunology* ; Gene Expression Profiling ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors*

Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic