Onco-critical care has emerged as an important subspecialty at the intersection of critical care medicine and oncology, attracting increasing attention in recent years. With continuous innovations in cancer therapies, patient survival has improved significantly; however, the incidence of associated critical complications has also increased. The reasons for cancer patients requiring intensive care unit admission are diverse and can be broadly categorized into three groups: progression of the underlying malignancy, treatment-related complications, and coexisting classical critical illnesses. Traditional critical care concepts and practices face limitations in addressing the multidimensional and heterogeneous challenges of onco-critical care. Based on the core mechanism of critical illness development—host/organ unregulated response (HOUR)—this article systematically elaborates on how this framework advances understanding and clinical practice into onco-critical care, with emphasis on its manifestations in neuroendocrine, immune-inflammatory, and coagulation-metabolic pathways. The review summarizes recent advances in clinical assessment and phenotyping systems for onco-critical illness and discusses a multidisciplinary, integrated management strategy centered on the "Disease Control, Host Response Modulation, Organ Support" triad. Finally, major challenges and future directions in this field are outlined. By integrating existing evidence and theoretical insights, this review aims to provide new perspectives and a theoretical foundation for the clinical management of onco-critical illness, thereby promoting its evolution toward precision and standardization.

Objective: To explore the association between serum nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), NIMA-related kinase 7 (NEK7) and pulmonary fibrosis among patients with coal workers' pneumoconiosis, so as to provide a basis for the assessment of the degree of pulmonary fibrosis. Methods: Coal workers with pneumoconiosis hospitalized in the Second Affiliated Hospital of Xuzhou Medical University from July 2022 to July 2023 were selected by simple random sampling. Data such as age, stage of pneumoconiosis, and dust-exposure duration were collected through the hospital's electronic medical record management system. Venous blood was collected to detect the levels of serum NLRP3 and NEK7. High-resolution computed tomography (HRCT) image data of the chest were obtained through the hospital's imaging reporting system. The left and right lungs were divided into 6 pulmonary regions according to the upper, middle, and lower parts. The pulmonary fibrosis score was quantified according to the proportion of the pulmonary area occupied by HRCT manifestations of pulmonary fibrosis, including reticular shadows, pleural and interlobular septal thickening, traction bronchiectasis, and honeycombing. The association between the levels of serum NLRP3, NEK7, and pulmonary fibrosis was analyzed using a multiple linear regression model. Results: A total of 81 patients with coal workers' pneumoconiosis were included, all of whom were male, with a mean age of (71.46±11.69) years. There were 48, 28, and 5 cases in stage Ⅰ, stage Ⅱ, and stage Ⅲ of pneumoconiosis pathological staging, accounting for 59.26%, 34.57%, and 6.17%, respectively. There were 45 cases of tunneling and coal mining, accounting for 55.56%. There were 41 cases with dust exposure years of ≥30 years, accounting for 50.62%. The median serum NLRP3 and NEK7 in patients with coal workers' pneumoconiosis were 2.01 (interquartile range, 2.33) ng/mL and 0.98 (interquartile range, 0.83) ng/mL. The median score of pulmonary fibrosis was 5.00 (interquartile range, 5.50) points. After adjusting for age, stage of pneumoconiosis, type of work and dust-exposure duration, multiple linear regression analysis showed that serum NLRP3 (β'=0.649) and NEK7 (β'=0.346) were positively correlated with the pulmonary fibrosis score. Conclusion The increase in the levels of serum NLRP3 and NEK7 in patients with coal workers' pneumoconiosis is related to the increase in the degree of pulmonary fibrosis.

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

This paper aimed to explore the effects of Duzhong Decoction(DZD)-containing serum on the proliferation and osteoblast differentiation of MC3T3-E1 cells through L-type voltage-gated calcium channels(L-VGCCs). L-VGCCs inhibitors, nifedipine and verapamil, were used to block L-VGCCs in osteoblasts. MC3T3-E1 cells were divided into a control group, a low-dose DZD-containing serum(L-DZD) group, a medium-dose DZD-containing serum(M-DZD) group, a high-dose DZD-containing serum(H-DZD) group, a nifedipine group, a H-DZD + nifedipine group, verapamil group, and a H-DZD + verapamil group. The CCK-8 method was used for cell proliferation analysis, alkaline phosphatase(ALP) assay kits for intracellular ALP activity measurement, Western blot for protein expression level in cells, real-time fluorescence quantitative PCR technology for intracellular mRNA expression level determination, fluorescence spectrophotometer for free Ca~(2+) concentration determination in osteoblasts, and alizarin red staining(ARS) for mineralized nodule formation in osteoblasts. The experimental results show that compared to the control group, DZD groups can promote MC3T3-E1 cell proliferation, ALP activity, and mineralized nodule formation, increase intracellular Ca~(2+) concentrations, and upregulate the protein expression of bone morphogenetic protein 2(BMP2), collagen Ⅰ(COL1), α2 subunit protein of L-VGCCs(L-VGCCα2), and the mRNA expression of Runt-related transcription factor 2(RUNX2), and BMP2. After blocking L-VGCCs with nifedipine and verapamil, the intervention effects of DZD-containing serum were inhibited to varying degrees. Both nifedipine and verapamil could inhibit ALP activity, reduce mineralized nodule areas, and downregulate the expression of bone formation-related proteins. Moreover, the effects of DZD-containing serum on increasing MC3T3-E1 cell proliferation, osteoblast differentiation, and Ca~(2+) concentrations, upregulating the mRNA expression of osteoprotegerin(OPG) and protein expression of phosphorylated protein kinase B(p-Akt) and phosphorylated forkhead box protein O1(p-FOXO1), and upregulating phosphatase and tensin homolog(PTEN) expression were reversed by nifedipine. The results indicate that DZD-containing serum can increase the Ca~(2+) concentration in MC3T3-E1 cells to promote bone formation, which may be mediated by L-VGCCs and the PTEN/Akt/FoxO1 signaling pathway, providing a new perspective on the mechanism of DZD in treating osteoporosis.
Animals ; Osteoblasts/metabolism* ; Cell Proliferation/drug effects* ; Cell Differentiation/drug effects* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Calcium Channels, L-Type/genetics* ; Alkaline Phosphatase/genetics* ; Serum/chemistry* ; Cell Line ; Osteogenesis/drug effects* ; Bone Morphogenetic Protein 2/genetics*

In recent years, there have been frequent adverse reactions/events associated with traditional Chinese medicine(TCM), especially liver injury related to traditional non-toxic TCM, which requires adequate attention. Liver injury related to traditional non-toxic TCM is characterized by its sporadic and insidious nature and is influenced by various factors, making its detection and identification challenging. There is an urgent need to develop a strategy and method for early detection and recognition of traditional non-toxic TCM-related liver injury. This study was based on national adverse drug reaction monitoring center big data, integrating methodologies such as reporting odds ratio(ROR), network toxicology, and computational chemistry, so as to systematically research the risk signal identification and evaluation methods for TCM-related liver injury. The optimized ROR method was used to discover potential TCM with a risk of liver injury, and network toxicology and computational chemistry were used to identify potentially high-risk TCM. Additionally, typical clinical cases were analyzed for confirmation. An integrated strategy of "discovery via big data, identification via dry/wet method, confirmation via typical cases, and precise risk prevention and control" was developed to identify the risk of TCM-related liver injury. Corydalis Rhizoma was identified as a TCM with high risk, and its toxicity-related substances and potential toxicity mechanisms were analyzed. The results revealed that liver injury is associated with components such as tetrahydropalmatine and tetrahydroberberine, with potential mechanisms related to immune-inflammatory pathways such as the tumor necrosis factor signaling pathway, interleukin-17 signaling pathway, and Th17 cell differentiation. This paper innovatively integrated real-world evidence and computational toxicology methods, offering insights and technical support for establishing a risk discovery and identification strategy for TCM-related liver injury based on real-world big data, providing innovative ideas and strategies for guiding the safe and rational use of medication in clinical practices.
Corydalis/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Chemical and Drug Induced Liver Injury/etiology* ; Medicine, Chinese Traditional/adverse effects* ; Rhizome/adverse effects* ; Male ; Female

Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the genus Aster (Asteraceae), has been reported to regulate the inflammatory response of macrophages in sepsis-induced acute lung injury. However, its function in post-stroke neuroinflammation, particularly microglia-mediated neuroinflammation, remains uninvestigated. This study found that SH significantly inhibited lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), in microglia in vitro. Furthermore, the results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which may be attributed to the inhibition of the microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited the phosphorylation of serine-threonine protein kinase B (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). These findings suggest that SH may be a potential therapeutic agent for relieving ischemic stroke (IS) by alleviating microglia-associated neuroinflammation.
Animals ; Microglia/immunology* ; Mice ; Male ; Mice, Inbred C57BL ; Brain Ischemia/immunology* ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotective Agents/administration & dosage* ; Interleukin-1beta/genetics* ; STAT3 Transcription Factor/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Proto-Oncogene Proteins c-akt/immunology* ; Nitric Oxide Synthase Type II/genetics* ; Lipopolysaccharides

Objective To investigate the effect of health failure mode and effect analysis(HFMEA)in optimizing the management process of postoperative diabetes insipidus in children undergoing neurosurgery.Methods Based on HFMEA,a management flowchart for postoperative diabetes insipidus in children undergoing neurosurgery was created.Brainstorming was adopted to identify failure modes in the workflow,analyze risk factors,and develop improvement measures,thereby refining the management flowchart.The amelioration and prognosis of diabetes insipidus in these children before(October 2022 to November 2023)and after(January 2024 to February 2025)implementation of the management flowchart were compared.Results The HFMEA-based management process for postoperative diabetes insipidus in children undergoing neurosurgery alleviated the symptoms of diabetes insipidus regarding the number of diabetes insipidus in the pediatric intensive care unit(P=0.006),the average daily urine output in the pediatric intensive care unit(P=0.001),the proportion of electrolyte abnormalities at discharge/transfer(P=0.037),the duration of mechanical ventilation(P=0.007),and the length of stay in the intensive care unit(P=0.001).Conclusion The HFMEA-based management process for postoperative diabetes insipidus in children undergoing neurosurgery is beneficial to the optimization of the management process,the alleviation of postoperative diabetes insipidus,and the improvement of prognosis in these children.
Humans ; Diabetes Insipidus/etiology* ; Neurosurgical Procedures/adverse effects* ; Child ; Postoperative Complications/therapy* ; Healthcare Failure Mode and Effect Analysis ; Intensive Care Units, Pediatric ; Risk Factors

OBJECTIVE: To investigate the clinical efficacy of moxibustion (Mox) combined with low-dose tadalafil (TAD) in the treatment of diabetes mellitus-induced erectile dysfunction (DMED) with the syndrome of Qi deficiency and blood stasis. METHODS: According to the inclusion and exclusion criteria, we selected 90 patients with DMED for this trial and equally randomized them into a Mox, a TAD, and a Mox combined with TAD (Mox+TAD) group to be treated by mild Mox applied to the acupoints Zusanli, Sanyinjiao and Yinlingquan qd alt, oral medication with low-dose TAD at 5 mg per dose qd, and combination of the above two therapies, respectively, all for 4 weeks. We obtained from the patients their IIEF-5 scores, traditional Chinese medicine (TCM) symptoms scores, Erectile Hardness Scale (EHS) scores, corpus cavernosal hemodynamic indexes, and the peak systolic velocity (PSV), end diastolic velocity (EDV) and resistance index (RI) of the corpus cavernosal arteries before and after treatment, and compared them among the three groups. RESULTS: The total effectiveness rate was significantly higher in the Mox+TAD (90.0%) than in the Mox (46.7%) and TAD groups (60.0%) (P< 0.05). Compared with the baseline, the IIEF-5 and EHS scores were increased, while the TCM symptoms scores decreased in all the three groups after treatment, more significantly in the Mox+TAD group than in the other two (P< 0.05). And the PSV and RI were remarkably increased, while the EDV decreased (P< 0.05) in all the three groups (P< 0.05) after treatment, with PSV even higher in the Mox+TAD than in the Mox and TAD groups (P< 0.05). CONCLUSION Moxibustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED, which can effectively improve the erectile function of the patients by increasing penile blood supply, benefiting qi and activating blood circulation.
Humans ; Male ; Tadalafil ; Erectile Dysfunction/etiology* ; Moxibustion ; Middle Aged ; Prospective Studies ; Adult ; Carbolines/administration & dosage* ; Diabetes Complications/therapy* ; Aged ; Treatment Outcome ; Combined Modality Therapy

BACKGROUND: Our understanding of the correlation between postdischarge cancer and mortality in patients with coronary artery disease (CAD) remains incomplete. The aim of this study was to investigate the relationships between postdischarge cancers and all-cause mortality and cardiovascular mortality in CAD patients. METHODS: In this retrospective cohort study, 25% of CAD patients without prior cancer history who underwent coronary artery angiography between January 1, 2011 and December 31, 2015, were randomly enrolled using SPSS 26.0. Patients were monitored for the incidence of postdischarge cancer, which was defined as cancer diagnosed after the index hospitalization, survival status and cause of death. Cox regression analysis was used to explore the association between postdischarge cancer and all-cause mortality and cardiovascular mortality in CAD patients. RESULTS: A total of 4085 patients were included in the final analysis. During a median follow-up period of 8 years, 174 patients (4.3%) developed postdischarge cancer, and 343 patients (8.4%) died. A total of 173 patients died from cardiovascular diseases. Postdischarge cancer was associated with increased all-cause mortality risk (HR = 2.653, 95% CI: 1.727-4.076, P < 0.001) and cardiovascular mortality risk (HR = 2.756, 95% CI: 1.470-5.167, P = 0.002). Postdischarge lung cancer (HR = 5.497, 95% CI: 2.922-10.343, P < 0.001) and gastrointestinal cancer (HR = 1.984, 95% CI: 1.049-3.750, P = 0.035) were associated with all-cause mortality in CAD patients. Postdischarge lung cancer was significantly associated with cardiovascular death in CAD patients (HR = 4.979, 95% CI: 2.114-11.728, P < 0.001), and cardiovascular death was not significantly correlated with gastrointestinal cancer or other types of cancer. CONCLUSIONS Postdischarge cancer was associated with all-cause mortality and cardiovascular mortality in CAD patients. Compared with other cancers, postdischarge lung cancer had a more significant effect on all-cause mortality and cardiovascular mortality in CAD patients.