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.

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.

Objective:To investigate the clinical features and prognostic factors of newly-treated elderly acute myeloid leukemia (AML) patients with intermediate-risk karyotype.Methods:A retrospective case series study was conducted. A total of 87 newly-treated elderly AML patients with intermediate-risk karyotype in the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from January 2013 to December 2023 were selected. The clinical characteristics were summarized. The Kaplan-Meier method was used for survival analysis and Cox proportional hazards model was used to make univariate and multivariate analyses of prognostic factors.Results:The median age [ M ( Q1, Q3)] of 87 patients was 69 (60, 87) years. The patients with normal karyotype and abnormal karyotype accounted for 77.1% (67/87), 22.9% (20/87), respectively. A total of 74 patients (85.1%) had 1 or more gene mutations, of which FLT3-ITD, NPM1 mutation, CEBPA mutation and WT1 high expression accounted for 29.9% (26/87), 26.4% (23/87), 19.5% (17/87), and 65.5% (57/87), respectively; additionally, 44.7% (39/87) of patients had 2 or more gene mutations. The objective response rate of patients after induction therapy was 47.7% (41/87), while the relapse rate was 73.2% (30/41). The median progression-free survival (PFS) time was 7.8 months, and the median overall survival (OS) time was 12.1 months. Univariate analysis result revealed that age, FLT3-ITD, hypomethylating agents, and minimal residual disease complete remission (MDR-CR) were factors influencing the OS of newly-treated elderly AML patients with intermediate-risk karyotype (all P < 0.05). Multivariate analysis indicated that MDR-CR was an independent risk factor for OS (yes vs. no: HR = 0.27, 95% CI: 0.14-0.51, P < 0.001). Conclusions:Newly-treated elderly AML patients with intermediate-risk karyotype have a high relapse rate and poor prognosis, and MDR-CR is identified as an independent influencing factor for the prognosis of these patients.

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.

MA Yueh-ch'ing (1906—1984), graduated from Peking Union Medical College in 1934, and became the first Chinese anesthetist hired by Peking Union Medical College Hospital in 1939. Based on the development and historical background of global anesthesiology, this article briefly introduces MA Yueh-ch'ing's personal experience and major achievements in anesthesiology.

Objective:To explore MRI T 2-mapping and blood oxygenation level dependent (BOLD) to evaluate the functional changes of paraspinal muscle in rats with discogenic low back pain (DLBP) after swimming. Methods:Totally 54 female 1-month-old SD rats were selected, which were divided into 3 groups by random number table method, sham operation (Sham) group, DLBP non-swimming group and DLBP swimming group, with 18 rats in each group. Under the guidance of X-ray fluoroscopy, the L4/5 and L5/6 intervertebral discs of the rats in the DLBP non-swimming group and DLBP swimming group were punctured by the posterior approach, and establishment of DLBP rat model by destroying nucleus pulposus, and only paraspinal muscles at the same level were punctured in the Sham group. After modeling, the DLBP swimming group received swimming exercise intervention for 5 consecutive days (30 min/d), while the DLBP non-swimming group and Sham group did not receive any rehabilitation exercise intervention. Each group was divided into 3 time point subgroups on average, the T 2-mapping and BOLD sequences were scanned at 30, 90 and 180 days after modeling to obtain the T 2 value, R 2* value of the paraspinal muscles, and the paraspinal muscles at the modeling level were taken for immunofluorescence staining, and the fluorescence intensity of myosin heavy chain (MYH)1 (type Ⅱ muscle fiber) and MYH7 (type I muscle fiber) was analyzed. One-way analysis of variance was used for comparison among the 3 groups, and the Bonferroni method was used for multiple comparisons, and Pearson correlation coefficient was used to evaluate the correlation between quantitative MRI parameters T 2 value, R 2* value and MYH1, MYH7 immunofluorescence intensity of rat paraspinal muscles at 180 days after modeling. Results:At 30 days after modeling, there was no significant difference in T 2 value and R 2* value among the 3 groups (all P>0.05). At 90 days after modeling, the T 2 value of the DLBP swimming group was higher than that of the DLBP non-swimming group, and the T 2 value of the DLBP non-swimming group was lower than that of the Sham group (all P<0.05), and there was no significant difference in the R 2* value among the 3 groups ( P>0.05). At 180 days after modeling, the T 2 value of the DLBP swimming group was higher than that of the DLBP non-swimming group, and the R 2* value was lower than that of the DLBP non-swimming group; the T 2 value of the DLBP non-swimming group was lower than that of the Sham group, and the R 2* value was higher than that of the Sham group (all P<0.05). At 30 and 90 days after modeling, there was no significant difference in the expressions of MYH1 and MYH7 among the 3 groups (all P>0.05). At 180 days after modeling, the expression of MYH1 decreased and the expression of MYH7 increased in the DLBP swimming group compared with the DLBP non-swimming group; the expression of MYH1 increased and the expression of MYH7 decreased in the DLBP non-swimming group compared with the Sham group (all P<0.05). At 180 days after modeling, the T 2 value had a moderate negative correlation with the fluorescence intensity of MYH1 ( r=-0.511, P=0.043), and a moderate positive correlation with the fluorescence intensity of MYH7 ( r=0.564, P=0.023); R 2* value was moderate positive correlated with the fluorescence intensity of MYH1 ( r=0.625, P=0.010), and moderate negative correlated with the fluorescence intensity of MYH7 ( r=-0.653, P=0.006). Conclusions:Swimming exercise can improve the reduction of water content and perfusion in the paraspinal muscles of DLBP rats, and reduce the transformation of muscle fibers from type Ⅰ to type Ⅱ, the changes of T 2 and R 2* value can reflect the transformation of paraspinal muscle fiber types to a certain extent.

Objective To preliminarily evaluate the application value of SpyGlass direct visualization system in the diagnosis and treatment of biliary stricture after liver transplantation. Methods Clinical data of 4 patients presenting with biliary stricture after liver transplantation who underwent SpyGlass direct visualization system examination were collected. The examination, treatment and prognosis of biliary stricture were analyzed. Results The examination results of color Doppler ultrasound, magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP) in 4 patients suggested biliary anastomotic stricture with intrahepatic biliary dilatation, and 2 of them were complicated with intrahepatic biliary calculi. Repeated placement of biliary stent under ERCP yielded poor effect in 3 cases. SpyGlass direct visualization system examination hinted biliary anastomotic stricture in 4 patients, 3 cases of intrahepatic biliary dilatation, 3 cases of intrahepatic biliary calculi, 2 cases of purulent bile and 3 cases of floccules within the biliary tract, 1 case of congestion and edema of biliary tract wall and 2 cases of local epithelial necrosis and stiffness changes of intrahepatic biliary tract wall. The wire could not be inserted in 1 patient due to severe biliary anastomotic stricture. Four patients were treated with biliary stricture resection + biliary stone removal + biliary end-to-end anastomosis, biliary stricture resection + biliary-intestinal anastomosis, ERCP lithotomy + biliary metal stent implantation, and biliary metal stent implantation + percutaneous transhepatic bile duct lithotomy, respectively. Relevant symptoms were relieved without evident complications. All patients survived during the follow-up until the submission date. Conclusions Compared with traditional imaging examination, SpyGlass direct visualization system may more directly display the morphological characteristics of biliary tract wall and structural changes within biliary tract cavity, which is an effective examination tool for biliary stricture after liver transplantation. In addition, individualized treatment methods may be adopted for different biliary tract diseases, which is expected to improve clinical prognosis of patients.