Sepsis is a systemic inflammatory response syndrome triggered by infection. It progresses rapidly and tends to develop into multiple organ dysfunction. Tanshinone ⅡA， one of the core active ingredients of Salvia miltiorrhiza， exerts remarkable targeted protective effects against sepsis-induced multiple organ dysfunction. This paper reviews the mechanisms by which tanshinone ⅡA alleviates sepsis-induced multiple organ dysfunction. Tanshinone ⅡA can relieve sepsis-induced lung injury by inhibiting the activity of Toll-like receptor 4/myeloid differentiation primary response protein 88/nuclear factor- κB， phosphatidylinositol 3-kinase/protein kinase B signaling pathways and maintaining mitochondrial homeostasis. It ameliorates sepsis- induced myocardial injury via suppressing the activation of NOD-like receptor family pyrin domain-containing 3/caspase-1 signaling pathway， downregulating the expression of inflammatory factors and regulating autophagy. It mitigates sepsis-induced renal injury by regulating oxidative stress imbalance and reducing the expression of apoptosis-related proteins. It alleviates sepsis-caused liver injury through inhibiting the release of inflammatory factors and hepatocyte apoptosis. It improves sepsis-induced intestinal barrier dysfunction by upregulating the expression of tight junction proteins and restraining inflammatory responses. Furthermore， it relieves sepsis-associated encephalopathy by activating peroxisome proliferator-activated receptor gamma coactivator-1α/nuclear respiratory factor 1/mitochondrial transcription factor A signaling pathway. Tanshinone ⅡA is expected to be a vital candidate drug for comprehensive prevention and treatment of sepsis. However， interdisciplinary research is required to break through current bottlenecks and realize the transformation from basic experiments to clinical application.

Background The health effects of environmental exposures are often characterized by complex interactions. However, evidence on the joint health effects of ambient oxidizing pollutants and air temperature in the cold regions of Northern China remains limited. Objective To examine the independent and interactive effects of atmospheric oxidizing pollutants and air temperature on daily mortality among residents of Hohhot. Methods Daily data on air quality, meteorological factors, and cause-specific mortality in Hohhot from 2018 to2023 were collected. A quasi-Poisson generalized additive model (GAM) combined with a distributed lag non-linear model (DLNM) was used to examine the effects of ambient oxidant pollutants [ozone (O₃), nitrogen dioxide (NO₂), and total oxidant (Oₓ)] and air temperature on daily circulatory and respiratory mortality. Potential interactions between oxidizing pollutants and temperature were evaluated using bivariate exposure–response surface models and quantified through stratified analyses. Results For each 10 μg·m⁻³ increase in O₃, O_X, and NO₂ concentrations, the strongest associations with circulatory disease mortality occurred at lag1, with excess risks (ERs) of 1.10% (95%CI: 0.50%, 1.71%), 1.84% (95%CI: 0.94%, 2.75%), and 1.49% (95%CI: 0.36%, 2.62%), respectively. The strongest associations of O₃ and O_X with respiratory disease mortality were observed at lag2, with ERs of 1.61% (95%CI: 0.61%, 2.62%) and 2.61% (95%CI: 1.61%, 3.62%), respectively. NO₂ showed the strongest cumulative association with respiratory disease mortality at lag02, with an ER of 3.22% (95%CI: 1.24%, 5.25%). High temperature exhibited immediate or short-term effects, while low temperature showed lagged effects. The exposure–response relationships between temperature and mortality risks for respiratory circulatory diseases were U-shaped. Positive additive interactions were observed between high temperature and high concentrations of O₃ and O_X. For the joint exposure to high temperature and high O₃, the relative excess risks due to interaction (RERIs) for circulatory and respiratory disease mortality were 0.131 (95%CI: 0.086, 0.176) and 0.279 (95%CI: 0.198, 0.360), respectively. For the joint exposure to high temperature and high O_X, the corresponding RERI values were 0.080 (95%CI: 0.038, 0.123) and 0.154 (95%CI: 0.074, 0.234), respectively. In contrast, high temperature and high NO₂ concentration exhibited antagonistic or attenuating interactions. Conclusion Ambient oxidizing pollutants, high temperature, and low temperature are independently associated with increased circulatory and respiratory disease mortality. High temperature combined with high concentrations of O₃ or O_X exerts positive additive interactions, with the respiratory system showing particular vulnerability. The mortality risks associated with NO₂ are more pronounced under low temperature conditions, whereas its interaction with high temperature appear antagonistic, suggesting a temperature-dependent risk-modifying effect.

Objective: To analyze the whole genome characteristics of Salmonella in diarrhea cases in Hohhot City, so as to provide the evidence for the prevention and control of Salmonella infection and rational clinical use of antibiotics. Methods: Salmonella strains were isolated and identified from fecal specimens of acute diarrhea cases at sentinel hospitals for national foodborne disease surveillance in Hohhot City from 2021 to 2023. DNA was extracted for whole genome sequencing. Bioinformatics analysis based on the Microobench Pathogen Genome Analysis System was conducted to determine serotypes, multi-locus sequence typing (MLST), drug resistance genes, and virulence genes. Additionally, 60 Salmonella genomic sequences from different regions across China were downloaded from the NCBI Genome database. A phylogenetic tree was constructed based on core-genome MLST (cgMLST) to analyze the phylogenetic relationship between strains from Hohhot City and those from other regions of China. Results: From 2021 to 2023, a total of 42 Salmonella strains isolated in Hohhot City were classified into 12 serotypes. Salmonella Enteritidis ST11, Salmonella I 4,[5],12:i:- ST34, and Salmonella Typhimurium ST19 were identified as the dominant strains, represented by 13, 10, and 6 isolates, which accounted for 30.95%, 23.81%, and 14.29%, respectively. Seventy-seven drug resistance genes belonging to 12 classes were detected. Among them, 17 Salmonella strains carried amino acid substitutions in the fluoroquinolone resistance-determining region caused by mutations at the gyrA and parC loci. Virulence genes covered all stages of Salmonella pathogenesis, with a predominance of genes associated with adhesion. Phylogenetic tree analysis results revealed that the 42 Salmonella strains from Hohhot City were distributed across evolutionary branches A, B, C, D, and F. They clustered with 60 strains from other regions of China, suggesting potential cross-regional transmission. Conclusions Salmonella strains isolated in Hohhot City exhibited diverse serotypes, carried multiple drug resistance genes and virulence genes, and displayed high genetic diversity. These findings indicate a potential risk of cross-regional transmission, highlighting the need for enhanced surveillance and prevention measures.

Objective:To explore the value of chromosomal microarray analysis (CMA) in the genetic diagnosis of different types of fetal growth restriction (FGR).Methods:A retrospective analysis was conducted on 120 cases who were diagnosed with FGR by ultrasound and underwent prenatal diagnosis at the Department of Obstetrics & Gynecology and Reproductive Medicine, Peking University First Hospital, from January 2016 to December 2021. The cases were divided into three groups based on the gestational age at the first diagnosis:<28 weeks (40 cases), 28-31 +6 weeks (65 cases), and ≥32 weeks (15 cases). They were also categorized into isolated and non-isolated FGR based on the presence of other ultrasound abnormalities (69 and 51 cases in each). Chromosomal karyotype analysis and CMA were conducted on all patients. The prenatal diagnosis results were analyzed, as well as the detection of chromosomal abnormalities in different gestational age groups and types of FGR. Statistical analysis was performed using Fisher's exact test. Results:(1) A total of 14 abnormalities were detected by CMA and four cases were detected by chromosomal karyotype analysis. The abnormal detection rate of CMA was higher than that of chromosomal karyotype analysis [11.7% (14/120) vs. 3.3% (4/120), P=0.025]. Among the total 14 cases of chromosomal abnormalities, there were seven pathogenic copy number variations (CNVs) and four variants of unknown significance (VUS), as well as two cases of trisomy-18 and one case of Turner syndrome. Among the 14 cases, eight had associated ultrasound abnormalities. Eleven of the 14 cases opted for induced abortion; three continued pregnancy to delivery, with two neonates showing no abnormalities and one exhibiting slightly delayed physical development. Both methods detected three cases of aneuploidy mnumber abnormalities (2.5%, 3/120) For chromosomal abnormalities <10 Mb, the detection rate of CMA was higher than that of chromosomal karyotype analysis [9.2% (11/120) vs. 0.8% (1/120), Fisher's exact, P=0.005]. Both methods detected one case of <10 Mb CNV, while CMA alone detected ten cases of <10 Mb microdeletions/microduplications (8.3%, 10/120), including six cases of pathogenic CNVs and four cases of VUS. (2) Among the 40 cases in the <28 weeks group, six cases (15.0%) of chromosomal abnormalities were detected, including three cases of aneuploidy, two cases of pathogenic CNVs, and one case of VUS. Among the 65 cases in the 28-31 +6 weeks group, seven cases (10.8%) of chromosomal abnormalities were detected, including five cases of pathogenic CNVs and two cases of VUS. Of the 15 cases in the ≥32 weeks group, one case of chromosomal abnormality was detected, which was VUS. (3) No statistically significant difference was found in the detection rate of chromosomal abnormalities between the isolated FGR and the non-isolated FGR groups [8.7%(6/69) vs. 15.7%(8/51), Fisher's exact, P=0.263]. (4) After excluding the ≥32 weeks non-isolated FGR group (only one case), the <28 weeks non-isolated FGR group had the highest detection rate of chromosomal abnormalities (1/18), while no abnormalities were detected in the ≥32 weeks isolated FGR group. Conclusions:Among FGR fetuses, the highest detection rates of chromosomal abnormalities are found in early-onset and non-isolated FGR. Prenatal diagnosis with CMA testing can significantly improve the detection rate of genetic causes in various types of FGR fetuses.

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 evaluate the efficacy and safety of adding toripalimab to bevacizumab and platinum-based chemotherapy as first-line treatment for refractory recurrent or metastatic (R/M) cervical cancer (CC). Methods: Patients were administered toripalimab (240 mg) + bevacizumab (7.5 mg/kg) combined with platinum-based chemotherapy once every three weeks for six cycles, followed by the maintenance therapy involving toripalimab + bevacizumab once every 3 weeks for 12 months or when disease progression or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were safety profiles, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Twenty-four patients were enrolled in this study and in the final analysis. The median follow-up duration was 18.6 (range, 3.3–28.5) months. The ORR was 83.3% (95% confidence interval [CI]=62.6–95.3) and the DCR was 95.8% (95% CI=78.9–99.9); 9 (37.5%) patients achieved complete response, 11 (45.8%) achieved partial response, and 3 (12.5%) had stable disease. The median PFS was 22.6 (95% CI=10.4–34.7) months and the median OS was not reached. The most common grade 3 treatment-related adverse events (AEs) were neutropenia (41.7%) and leukopenia (16.7%). The most common immune-related AEs (irAEs) were thyroid dysfunction (37.5%) and increased adrenocorticotropic hormone (37.5%) and serum cortisol levels (33.3%). No grade ≥3 irAEs were observed. Conclusion Toripalimab combined with bevacizumab and platinum-based chemotherapy show promising clinical efficacy and favorable safety profile, providing an alternative firstline treatment option for patients with R/M CC.

Objective:To construct a prior based on the inherent properties of PET to accurately segment the lesion areas.Methods:A network framework for PET tumor segmentation driven by geodesic priors was proposed (geodesic network for short). Specifically, partial differential equations were constructed to characterize the geodesic distances between different regions in PET images. Tumor marker points identified by CT labeling were used as the initial conditions for the equations. To enhance the contrast between areas of lung or breast tumors and normal tissues, a smooth Heaviside function was utilized to map the geodesic distances. The network framework adopted a dual-branch architecture, using geodesic priors to assist in PET image segmentation.Results:The proposed method achieved a Dice coefficient of 94.92% in lung cancer segmentation and 90.12% in breast cancer segmentation. With the addition of geodesic priors in the Unet, the Dice coefficient for breast cancer increased by 32.37% (from 42.50% to 74.87%).Conclusion:Geodesic priors can significantly improve segmentation outcomes and enhance the generalization capability of the network.

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 understand nurses' experiences providing discharge preparation services for elderly patients with multiple chronic diseases and offer references for developing intervention strategies for discharge preparation services for these patients.Methods:A purposive sampling method was used to select 24 nurses from the cardiovascular departments, geriatrics wards, and other internal medicine departments of three Grade A tertiary hospitals, four Grade B hospitals, and one community health service center in Guilin City between March and April 2024. An interview outline was developed based on the social-ecological system theory, and semi-structured interviews were conducted to collect data. A directed content analysis method was used to analyze the data.Results:A total of three themes were identified: micro-level (nurses have a positive attitude but face shortcomings in age-appropriate discharge preparation services), meso-level (team collaboration mechanisms are weak), and macro-level (there is a desire to link social resources) .Conclusions:Nurses' discharge preparation services for elderly patients with multiple chronic diseases are inadequate. It is recommended to enhance nurses' discharge preparation skills through core competency-based training, improve the development of innovative healthcare platforms, and promote establishing of a multi-dimensional social care support system to improve the quality of discharge preparation services for elderly patients with multiple chronic diseases.

Objective:To investigate the spatial and temporal distribution characteristics of brucellosis in Heilongjiang Province, Jilin Province and Inner Mongolia Autonomous Region (hereafter referred to as the Hei-Ji-Meng province and region), and study the influencing factors of brucellosis incidence.Methods:Using a retrospective analysis method, the data of brucellosis incidence in 22 prefecture-level cities in the Hei-Ji-Meng province and region from 2014 to 2018, as well as the data of natural environmental factors (precipitation, temperature, relative humidity, solar radiation, wind speed, vegetation index) and social environmental factors (livestock breeding, livestock and poultry meat production, cultivated land area) were collected and integrated. The spatial autocorrelation model and spatial Dubin model were used to analyze the spatial and temporal distribution rule of brucellosis and the impact of environmental factors on the incidence of brucellosis in prefecture-level cities.Results:From 2014 to 2018, the incidence of brucellosis in the Hei-Ji-Meng province and region was 18.77/100 000, among which the incidence in Inner Mongolia Autonomous Region was 33.45/100 000, followed by Heilongjiang Province (13.67/100 000) and Jilin Province (6.57/100 000). Among all prefecture-level cities, the brucellosis incidence was relatively higher in Hinggan League of Inner Mongolia Autonomous Region (69.10/100 000). Except 2016, the brucellosis incidence in other years had a positive spatial correlation (global Moran's I > 0, P < 0.05). The high-high concentration aggregation pattern was mainly concentrated in Ulanqab City, Xilingol League, Chifeng City, Tongliao City, Hinggan League, Hohhot City, and Hulunbuir City of Inner Mongolia Autonomous Region. Among the environmental factors related to brucellosis, cultivated land area and sheep breeding density had a positive effect on brucellosis incidence in the local area, with the effect intensity of 0.39 and 0.32, respectively ( P < 0.001). The average humidity from April to July had a negative effect on the brucellosis incidence in the local area, with the effect intensity of - 0.22 ( P = 0.023). The indirect effect of the number of pigs slaughtered on the brucellosis incidence in adjacent areas was the most significant, and the effect intensity was 2.15 ( P < 0.001). Conclusions:Among the Hei-Ji-Meng province and region, the annual average incidence rate of brucellosis in Inner Mongolia Autonomous Region is relatively higher, and the high-high concentration areas are mainly concentrated in this region. Among the environmental factors, the cultivated land area, sheep breeding density, the average humidity from April to July and the number of pigs slaughtered have an impact on brucellosis incidence.