Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is the primary cause of mortality in sepsis, with its core pathophysiological mechanism being severe ischemia and hypoxia in critical units—composed of microcirculation and the mitochondria of functional cells—resulting from disruptions in blood flow and oxygen flow following a dysregulated host response. Due to the systemically convergent yet clinically heterogeneous nature of the host response, current understanding and management strategies for hemodynamics remain inconsistent, often leading to inadequate resuscitation or overtreatment. To improve the quality of care, based on a systematic review of the "blood flow-oxygen flow" theory, an expert panel emphasizes reevaluating septic shock from an integrated perspective of blood flow and oxygen flow, and has formulated the Expert Consensus on Blood Flow and Oxygen Delivery Phenotyping and Clinical Management of Septic Shock (2025). The consensus proposes that clinical typing of blood flow-oxygen flow should comprehensively consider cardiac function, vascular tone, oxygen flow utilization status in critical units, and disease trajectory, while optimizing subtype identification by integrating host response phenotypes and artificial intelligence technologies. It advocates establishing a continuous assessment system through multi-site oxygen flow monitoring for organ perfusion, peripheral perfusion monitoring, and critical care ultrasound. Under the framework of the "critical care triangle", the consensus promotes the implementation of individualized, bundled management strategies, providing guidance for multiple management points to restore blood flow-oxygen flow matching, reduce the risk of organ failure, and decrease patient mortality.

With the rapid advancement of hemodynamic indices and monitoring technologies, their classification methods and application processes have become increasingly complex. Currently, no unified standard hasbeen established, making it difficult to fully meet the clinical requirements for hemodynamic management. To assist in hemodynamic monitoring assessment and therapeutic decision-making in critically ill patients, the Critical Hemodynamic Therapy Collaborative Group, in conjunction with the Critical Ultrasound Study Group, has jointly developed the Standard for the Application of Hemodynamic Monitoring Techniques in Critical Care. The first part of this standard systematically categorizes hemodynamic indicators into flow indicators, pressure and its derivative indicators, and tissue perfusion indicators, while elaborating on the clinical application of each. The second part establishes a standardized clinical implementation pathway for hemodynamic monitoring. It proposes a tiered monitoring strategy-comprising basic, advanced, indication-specific, and special scenario monitoring-tailored to different clinical settings. It emphasizes the central role of critical care ultrasound across all levels of monitoring and establishes hemodynamic assessment standards for organs such as the brain, kidneys, and gastrointestinal tract. This standard aims to provide a unified framework for clinical practice, teaching, training, and research in critical care medicine, thereby promoting standardized development within the discipline.

Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC_{50, SMS2} = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t _{1/2, cornea} = 1.11 h; t _{1/2, meibomian glands} = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.

Diseases of ocular fundus are the leading causes of severe vision impairment or even blindness in patients worldwide, and the medical treatments are seriously limited by the difficulty of therapeutic drugs entering the fundus due to the various physiological barriers. Nano-drug delivery systems, with their nanoscale size and large surface area, can be loaded with therapeutic drugs of different physicochemical properties and modified with various surface active substances, which can not only improve the solubility and penetration of the drugs, but also protect biologic drugs from degradation and improve the biological safety and bioavailability, as well as deliver therapeutic drugs to specific ocular targets. All of these make the therapeutic potential enormous. Currently, more and more studies have been carried out to take advantage of nanomaterials for the treatment of different fundus diseases, including neurodegenerative diseases, fundus neovascularization, endophthalmitis and fundus tumors. This review analyzes the challenges and barriers faced by different routes of drug administration in the treatment of fundus diseases, the physicochemical properties of common nano-drug delivery systems that have been studied in related fields, and further summarizes the progress, advantages, limitations, and future directions of the application of various nano-drug delivery systems for the treatment of ocular fundus diseases in recent years.

Objective:To investigate the effects of Houttuynize Herba decoction on aspirin-induced gastric ulcer (GU) in mice; To discuss its mechanism.Methods:A total of 64 SPF male mice were selected, and 48 mice were randomly selected to establish the model by gavage of 20 mg/ml aspirin solution. The remaining 16 rats were treated as normal group by gavage with the same amount of normalsaline once a day for 7 consecutive days. After successful modeling, the remaining mice in the model group were randomly divided into 5 groups, with 8 mice in each group, namely normal saline group (given normal saline), omeprazole group (given omeprazole 0.5 mg/ml), Houttuynize Herba high-, medium- and low-dosage groups (given 1.08 g/ml, 0.54 g/ml, 0.27 g/ml), and the remaining 8 mice in the normal group were given the same amount of normal saline by gavage. The mice were treated by gavage once a day for 7 days. The number of Escherichia coli and Bifidobacterium in mouse feces was counted by bacterial culture method, and the ratio of Bifidobacterium to Escherichia coli (B/E value) was used to judge the imbalance of bacterial flora. The expression of interleukin-6 (IL-6) in serum was detected by magnetic particle chemiluminescence. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of prostaglandin E 2 (PGE 2) in the serum of mice to determine the level of inflammation. Hematoxylin-eosin staining was used to determine the ulcer and healing. ImageJ 1.8.0 was used to calculate the ulcer inhibition rate. The protein expression levels of IκBα, NF-κB-p65 subunit and phosphorylated IκBα (p-IκBα) and p65 (p-NF-κB-p65) subunits in gastric tissue of mice were evaluated by Western blot. Results:Compared with the normal group, the epithelial cells of the gastric mucosa were missing, the glands were irregularly arranged, and the tissue structure was severely damaged in the modeling group; the number of Escherichia coli in the intestine increased ( P<0.01), the number of Bifidobacterium decreased ( P<0.01), and the B/E value was less than 1 ( P<0.01); Serum PGE2 levels were decreased ( P<0.01), IL-6 levels were increased ( P<0.01); The expression of p-IκBα and p-NF-κB-p65 proteins in gastric tissues was elevated ( P<0.05). After 7 days of drug treatment, compared with the saline group, gastric mucosal cells and structures were improved, and weight gained in the Houttuynize Herba groups ( P<0.05); the rate of inhibition of ulcers in mice in the Houttuynize Herba high-dosage group was significantly improved ( P<0.01); the number of Bifidobacteria in the intestinal tract significantly increased ( P<0.01), that of Escherichia coli was diminished ( P<0.05), B/E value was greater than 1 ( P<0.05), IL-6 content in peripheral blood was reduced ( P<0.05), PGE 2 levels significantly increased ( P<0.01); the level of p-IκBα/IκBα and p-NF-κB-p65/NF-κB-p65 in the gastric tissues of mice decreased ( P<0.01). Conclusion:Houttuynize Herba decoction can effectively improve gastric mucosal injury in mice, and its mechanism may be related to regulating intestinal microorganisms, inhibiting the opening of IκBα/NF-κB pathway, and reducing inflammatory response.

Objective:To explore the feasibility of predicting complexity of intensity modulated radiotherapy(IMRT)plan through adopted machine learning method to extract planomics features of radiotherapy,so as to provide a new method for comprehensive evaluation of the complexity of IMRT plan.Methods:The medical case data of 3203 patients with pelvic tumor,or abdominal tumor or head and neck tumor,who admitted to The First Affiliated Hospital with Nanjing Medical University from December 2022 to November 2023,were selected.All patients adopted Monaco system to conduct design for plan,and underwent treatment on Precise and Axesse accelerators.The evaluation indicator of complexity of 10 plans was calculated by using Python software,and the planomics features in the files of radiotherapy plans were extracted through format conversion and pyradiomics tool of imaging omics.The planomics features of radiotherapy were selected through data cleaning,filtering method and embedding method of machine learning.The corresponding predictive model of the evaluation indicator of complexity of 10 common plans was respectively constructed through used Gradient Boosting Decision Tree algorithm.The goodness of fit(R2)was adopted to evaluate the prediction performance of the model,and the 5-fold cross-validation method was adopted to detect the generalization ability of the model.Results:There were statistically significant differences between Precise accelerator and Axesse accelerator in average leaf to area(LA),plan irregularity(PI)of beam shape and standard circle,modulation complexity score(MCS)of the variability between shape and area of subfield,and the advantage value of leaf travel(LT)(t=63.894,-63.678,72.582,-48.858,P＜0.01),respectively.A total of 107 planomics features were extracted through pyradiomics tool,and 38 features were remained after filtering method conducted screening,and 4 to 11 features were remained after embedding method conducted screening.The goodness of fits of mean field area(MFA),LA and leaf gap average(LGA)value were better in the validation set,with R2＞0.970,however the goodness of fits of the proportion of small aperture score 20 mm(SAS20)was poor in validation set,with R2=0.917.The 5-fold cross-validation results showed that the average value of prediction accuracy of all indicators of complexity was＞90％.Conclusions:The extracted planomics features of radiotherapy based on radiomics method can accurately predict the complexity of IMRT plan,which are expected to play a greater role in improving the ensure efficiency of individual quality of patient,and screening radiotherapy plan with higher-quality.

Objective:To investigate the incidence and mortality of breast cancer in tumor registration areas of Shanxi Province in 2019.Methods:A cross-sectional study was conducted. The tumor registration data reported by 13 tumor registration areas in Shanxi Province in 2019 were collected, and the overall incidence and mortality of breast cancer were analyzed. The stratified analysis was conducted by gender and region, and the incidence, mortality, accumulation rate (0-74 years old), age-specific incidence rate, age-specific mortality rate, Chinese population standardized rate and world population standardized rate were calculated. The standard population was based on the 2000 China population census standard population composition and Segi world standard population composition.Results:In 2019, there were 871 new cases of breast cancer in the tumor registration areas of Shanxi Province, with an incidence rate of 17.83/100 000, and 202 deaths, with a mortality rate of 4.13/100 000. The age-specific incidence of breast cancer was at a low level in 0-25 years old, it increased rapidly after 30 years old, and reached a peak in people aged 60 years old. The age-specific mortality showed a slow rising trend with the increase of age, and increased rapidly in people over 75 years old. The age-specific incidence and mortality of breast cancer in female were higher than those in male. Although the general trend of change concerning urban and rural age-specific incidence was similar, the trend of change concerning urban and rural age-specific mortality had their own characteristics. In 4 urban tumor registration areas, the highest male and female Chinese population standardized incidence rates were found in Yuci District of Jinzhong City (0.62/100 000) and Yangquan City (41.86/100 000). Male Chinese population standardized mortality rate was 0/100 000, and the highest female Chinese population standardized mortality rate was found in Yangquan City (12.62/100 000). In 9 rural tumor registration areas, the highest male and female Chinese population standardized incidence rates were found in Jishan County (2.59/100 000) and Pingding County (36.42/100 000). The highest Chinese population standardized mortality rates were found in Yuanqu County (0.89/100 000) and Jishan County (4.82/100 000).Conclusions:Women, urban area people and middle-aged and elderly people are the foci of breast cancer prevention and control in Shanxi Province.

Objective:To analyze the role of dandelion and mulberry leaf in the progression of acute myeloid leukemia(AML)by network pharmacology,and to clarify the active components and their mechanisms in treating AML.Methods:The active components of dandelion and mulberry leaf were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).The targets were predicted by SwissTargetPrediction Database.The AML-related genes and protein targets were retrieved from the SymMap Database,the GeneCards Human Gene Database,the DisGeNET Database,and the Online Mendelian Inheritance in Man(OMIM)Database.The AML-related genes and target genes of dandelion and mulberry leaf were compared by comparative analysis and were identify by the enrichment genes,followed by Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis.The drug-active component-target network and protein-protein interaction(PPI)network were constructed by Cytoscape 3.8.0 software,and the core genes were selected by CytoNCA plugin;the molecular docking was conducted by AutoDock software.Results:After filtering by databases,39 active components were identified,and 148 common targets between dandelion-mulberry leaf and AML were collected.The GO functional enrichment analysis mainly involved cytokine-mediated signaling pathways,positive regulation of kinase activity,and oxidative stress responses.The KEGG signaling pathway enrichment analysis focused on the phosphatidylinositol 3 kinase/protein kinase B(PI3K-AKT)signaling pathway,the tumor necrosis factor(TNF)signaling pathway,and the Janus kinase/signal transducer and activator of transcription(JAK-STAT)signaling pathway.The key targets were identified by topological analysis including signal transducer and activator of transcription 3(STAT3),epidermal growth factor receptor(EGFR),protein kinase B1(AKT1),recombinant human epidermal growth factor(EGF),vascular endothelial growth factor A(VEGFA),oncogene MYC,tumor protein P53(TP53),mitogen-activated protein kinase 3(MAPK3),cysteiny asparate specific protease-3(CASP3),oncogene SRC,heat shock protein 90 alpha family class A member 1(HSP90AA1),tenascin XB1(CTNNB1),phosphoinositide kinase-3 catalytic subunit alpha(PIK3CA),interleukin 6(IL-6),TNF,mitogen-activated protein kinase 1(MAPK1),and phosphatidylinositide kinase-3 regulatory subunit 1(PIK3R1).The molecular docking results showed the highest affinity pairing to be taraxerol with MYC(-8.74 kcal·mol-1),and quercetin,kaempferol,luteolin,and artemetin demonstrated good binding affinities with various targets.Conclusion:The main active components of dandelion-mulberry leaf,such as quercetin,taraxerol,kaempferol,luteolin,and artemetin,may exert the anti-AML effect by regulating AKT1,STAT3,HSP90AA1,IL-6,and MAPK1;regulation the PI3K-AKT signaling pathway may be the critical mechanism of anti-AML effect by dandelion-mulberry leaf.

Objective:To investigate the risk factors for intraoperative hemorrhage during endoscopic submucosal dissection (ESD) for colorectal lesions.Methods:Data of 386 patients with colorectal lesions, who underwent ESD at The Third People's Hospital of Datong and its cooperative hospital, Nanjing Drum Tower Hospital, from December 2019 to August 2021 were retrospectively analyzed. The patients were divided into the hemorrhage group ( n=85) and the non-hemorrhage group ( n=301) according to intraoperative hemorrhage. The correlationship of patients'basic information, lesion-related factors and hemorrhage during colorectal ESD was analyzed. Univariate and multivariate logistic regression were used to identify the risk factors for intraoperative hemorrhage during ESD. The risk predictive model of intraoperative hemorrhage during ESD was established according to the screened risk factors, and receiver operator characteristic (ROC) curve was used to evaluate the predictive model. Results:Univariate logistic regression showed that a history of diabetes ( OR=2.340, P<0.05), a history of coronary atherosclerotic heart diseases ( OR=3.100, P<0.05), the lesion located in the rectum ( OR=3.272, P<0.05), longer lesion ( OR=1.093, P<0.05), wider lesion ( OR=1.057, P<0.05), larger lesion ( OR=1.126, P<0.05), depressed lesion ( OR=6.128, P<0.05), the laterally spreading lesion ( OR=2.651, P<0.05), the lesion infiltrated into the SM-S layer ( OR=0.088, P<0.05), the lesion infiltrated into the SM-D layer ( OR=0.174, P<0.05), the diameter of hemorrhage vessels 0.5~<1.0 times of the diameter of incision knife ( OR=246.854, P<0.05), the postoperative pathology as early cancer ( OR=7.000, P<0.05) were risk factors for intraoperative hemorrhage during ESD. Considering the quantitative relationship between the length, the width and the area of lesions, multi-factor models were constructed using the length and area of lesions respectively. Forward stepwise regression was used to screen variables and determine the final model, and the results showed that a history of coronary atherosclerotic heart diseases, the depressed lesion, the longer lesion, the larger lesion, the diameter of hemorrhage vessels 0.5~<1.0 times of the diameter of the incision knife were independent risk factors for intraoperative hemorrhage during ESD. The two modeling results of the lesion length and the lesion area were very similar. Therefore, lesion length was recommended to describe lesions in clinical practice. Conclusion:A history of coronary atherosclerotic heart disease, the depressed lesion, the longer lesion, the larger lesion, the diameter of vessels 0.5~<1.0 times of that of the incision knife are independent risk factors for intraoperative hemorrhage during ESD.