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.

This study systematically collated and textual researched realgar from aspects such as name,origin,and quality by consulting ancient herbal texts,classic medical books,and modern literature.The textual research shows that current herbal works all take"realgar"as the official name,with aliases including"Huangshi shi","Shihuang","Tianyang shi","Jiguan shi","Xunhuang","Chouhuang",and"Mingxiong",etc.Ancient herbal records indicate that Xunhuang,Chouhuang,and Shuiku Realgar are all Realgar,while Orpiment is its associated mineral.In ancient times,the main production areas of Realgar were in Gansu,with outputs also seen in Shandong and Hunan.Nowadays,it is mainly produced in Hunan,Guizhou,Hubei,Gansu,Yunnan,Sichuan and other regions.Ancient herbal works mentioned characteristics like"cockscomb color","non-stinky","solid","red and bright"in their quality evaluation,while modern herbal works mostly evaluate its quality by color and texture,such as"red color","large blocks","brittle texture","glossy".The traditional efficacy of Realgar is to dry dampness,kill insects,detoxify various poisons,treat sores and activate blood.Modern studies have shown it also has anti-tumor,antibacterial and antiviral effects.Processing methods in past dynasties included water grinding,vinegar processing,refining,etc.,and currently,water grinding and acid water grinding are commonly used.This paper observed the properties of Realgar,detected the content of As?S?,and analyzed the microscopic characteristics and far-infrared spectral characteristics of qualified batches of Realgar.It was finally found that the As?S? content of qualified batches of Realgar was all more than 90%;under the scanning electron microscope,it showed massive shape,uniform distribution,obvious particles,and no agglomeration;a small amount of associated mineral Orpiment crystals were observed under the polarizing microscope;the characteristic peaks of Realgar(343-344 cm?1,224-225 cm?1,372-374 cm?1,367-369 cm?1,359 cm?1,207-208 cm?1,193-194 cm?1,168-170 cm?1)and Orpiment(390 cm?1,380 cm?1,347 cm?1,311 cm?1,300 cm?1,201 cm?1,182 cm?1,158 cm?1 and 139 cm?1)were determined."Red color and glossy"can be used as property references,"Realgar is a sulfide mineral of the Realgar family,with the main chemical component As?S?,associated with Orpiment"can be used as origin references,and"Shimen in Hunan,Wanshan in Guizhou,Yunnan,Gansu,Sichuan"can be used as production area references,which are consistent with the results of herbal textual research.This study provides a basis for the identification and analysis of Realgar,with a view to better guiding clinical medication and resource utilization.

This study systematically collated and textual researched realgar from aspects such as name,origin,and quality by consulting ancient herbal texts,classic medical books,and modern literature.The textual research shows that current herbal works all take"realgar"as the official name,with aliases including"Huangshi shi","Shihuang","Tianyang shi","Jiguan shi","Xunhuang","Chouhuang",and"Mingxiong",etc.Ancient herbal records indicate that Xunhuang,Chouhuang,and Shuiku Realgar are all Realgar,while Orpiment is its associated mineral.In ancient times,the main production areas of Realgar were in Gansu,with outputs also seen in Shandong and Hunan.Nowadays,it is mainly produced in Hunan,Guizhou,Hubei,Gansu,Yunnan,Sichuan and other regions.Ancient herbal works mentioned characteristics like"cockscomb color","non-stinky","solid","red and bright"in their quality evaluation,while modern herbal works mostly evaluate its quality by color and texture,such as"red color","large blocks","brittle texture","glossy".The traditional efficacy of Realgar is to dry dampness,kill insects,detoxify various poisons,treat sores and activate blood.Modern studies have shown it also has anti-tumor,antibacterial and antiviral effects.Processing methods in past dynasties included water grinding,vinegar processing,refining,etc.,and currently,water grinding and acid water grinding are commonly used.This paper observed the properties of Realgar,detected the content of As?S?,and analyzed the microscopic characteristics and far-infrared spectral characteristics of qualified batches of Realgar.It was finally found that the As?S? content of qualified batches of Realgar was all more than 90%;under the scanning electron microscope,it showed massive shape,uniform distribution,obvious particles,and no agglomeration;a small amount of associated mineral Orpiment crystals were observed under the polarizing microscope;the characteristic peaks of Realgar(343-344 cm?1,224-225 cm?1,372-374 cm?1,367-369 cm?1,359 cm?1,207-208 cm?1,193-194 cm?1,168-170 cm?1)and Orpiment(390 cm?1,380 cm?1,347 cm?1,311 cm?1,300 cm?1,201 cm?1,182 cm?1,158 cm?1 and 139 cm?1)were determined."Red color and glossy"can be used as property references,"Realgar is a sulfide mineral of the Realgar family,with the main chemical component As?S?,associated with Orpiment"can be used as origin references,and"Shimen in Hunan,Wanshan in Guizhou,Yunnan,Gansu,Sichuan"can be used as production area references,which are consistent with the results of herbal textual research.This study provides a basis for the identification and analysis of Realgar,with a view to better guiding clinical medication and resource utilization.

Objective·To determine hyaluronan(HA)expression in the endocrine-resistant microenvironment of estrogen receptor-positive(ER+)breast cancer and elucidate its impact on the acquired resistance.Methods·Chemiluminescent immunoassay was used to quantify HA levels in the culture supernatants of fulvestrant-resistant breast cancer cells.An immunofluorescence(IF)assay was performed to visualize the colocalization of CD44 and HA in MCF7/FulR cells.Using an established adaptive endocrine-resistant breast cancer mouse model,HA expression in resistant breast cancer tissues was assessed by immunohistochemistry(IHC)assay.Single-cell RNA sequencing(scRNA-seq)and RNA sequencing(RNA-seq)were conducted to examine transcriptomic profiles and alterations in HA-related genes in resistant breast cancer cells.Flow cytometry(FCM)was utilized to measure the proportion of CD44+CD24-cells in MCF7/FulR.The correlation between HA synthesis genes and cell stemness was investigated in clinical ER+breast cancers from GEO data sets.Hyaluronidase(HAase)treatment was applied to remove the"HA coat",and RT-qPCR and Western blotting analysis were carried out to monitor changes in stemness-related molecules.CCK-8 assays,flow cytometry(FCM),and Hoechst 33258 staining were performed to determine changes in apoptosis and fulvestrant efficiency after HAase treatment.Results·IF results revealed that compared with MCF7 cells,the"HA coat"on the surface of MCF7/FulR cells was significantly thickened.IHC demonstrated markedly increased HA retention in fulvestrant-resistant mouse breast cancer tissues.ScRNA-seq and RNA-seq analyses indicated elevated expression of stemness-related genes and HA synthesis-associated genes in fulvestrant-resistant breast cancer cells.Correlation analysis revealed a positive association between HA synthesis and cancer stemness in ER+breast cancer.IF and RT-qPCR results demonstrated that removing the HA coating from the surface of MCF7/FulR cells led to a significant reduction in the expression of stemness-related molecules;concurrently,CCK-8 assays,FCM analysis,and Hoechst 33258 staining revealed that"HA coat"clearance reduced MCF7/FulR'tolerance to fulvestrant and increased apoptosis.Conclusion·Endocrine-resistant breast cancer cells develop an enriched"HA coat",which promotes stemness in fulvestrant-resistant tumors.Disruption of this HA coat through HAase treatment effectively reduces cell stemness,induces apoptosis,and re-sensitizes breast cancer cells to fulvestrant.

Pancreatic cancer(PC)is a highly malignant digestive system tumor with extremely high mortality and recurrence rates.While traditional surgical resection and chemotherapy remain the main treatment options,challenges such as high postoperative recurrence and poor prognosis persist.Therefore,exploring more effective comprehensive treatment strategies is crucial for improving patient survival and prognosis.This review systematically summarizes recent advances in systemic therapy for PC,with a focus on the application and efficacy of chemotherapy,targeted therapy,and immunotherapy.Additionally,it discusses the potential of neoadjuvant therapy,integrated traditional Chinese and Western medicine approaches,and conversion therapy in enhancing the effects of conventional chemotherapy.Studies have shown that targeted therapy can enhance antigen presentation and reduce side effects,while immune checkpoint inhibitors,cancer vaccines,and adoptive cell immunotherapy help mitigate tumor immune evasion and improve the tumor microenvironment.Despite continuous innovation in treatment approaches,clinical management of PC,particularly for advanced-stage patients,still faces significant challenges.Future research should focus on early diagnosis,precision medicine,and personalized treatment strategies to further improve cure rates and patient survival quality,providing more effective therapeutic options for clinical practice.

Objective:To investigate the application value of dermoscopy and reflectance confocal microscopy (RCM) in identifying field cancerization in actinic keratosis (AK) in the elderly.Methods:A retrospective analysis was conducted on clinical, dermoscopic, and RCM features of elderly (> 60 years old) patients, who were confirmedly diagnosed with AK and had complete medical records at Shanghai Skin Disease Hospital from January 2022 to December 2023.Results:A total of 132 elderly patients with AK were included. Dermoscopy showed brownish-gray pseudonetwork pigment patterns, follicular horn plugs, irregular branched vessels, and rosette signs in AK lesions. Histopathological examination in 51 patients revealed that 47 (92.16%) were confirmedly diagnosed with AK. Field cancerization was observed in 106 patients (80.3%), among whom 66 (62.26%) had irregular branched vessels, 88 (83.02%) predominantly exhibited brownish-gray pseudonetwork pigment patterns, and 83 (78.30%) showed scattered brown pigment networks/fingerprint-like patterns. Post-treatment follow-up of 63 patients showed varying degrees of changes in vascular and pigment structures by dermoscopy, with significant reductions in follicular horn plugs and superficial yellow-white scales or keratin masses. RCM examinations in 41 AK patients all showed disordered arrangements of keratinocytes presenting as atypical honeycomb patterns, with atypical cells in the AK lesions; in the field cancerization areas of 20 patients, RCM revealed keratinocytes disorderedly arranged in an irregular honeycomb pattern, with some keratinocytes exhibiting mild atypia. Thirty-four AK patients underwent dynamic RCM monitoring before and after 1, 3 and 6 months of ALA-PDT treatment, which showed gradual regularization of arrangements of keratinocytes and reduction of atypical cells, as well as reappearance of atypical keratinocytes upon recurrence.Conclusions:The incidence of field cancerization was relatively high in elderly AK patients. Dermoscopy and RCM are helpful for the early identification of AK and field cancerization, especially in patients with multiple lesions and with difficulties in multi-site biopsy.

Objective·To determine hyaluronan(HA)expression in the endocrine-resistant microenvironment of estrogen receptor-positive(ER+)breast cancer and elucidate its impact on the acquired resistance.Methods·Chemiluminescent immunoassay was used to quantify HA levels in the culture supernatants of fulvestrant-resistant breast cancer cells.An immunofluorescence(IF)assay was performed to visualize the colocalization of CD44 and HA in MCF7/FulR cells.Using an established adaptive endocrine-resistant breast cancer mouse model,HA expression in resistant breast cancer tissues was assessed by immunohistochemistry(IHC)assay.Single-cell RNA sequencing(scRNA-seq)and RNA sequencing(RNA-seq)were conducted to examine transcriptomic profiles and alterations in HA-related genes in resistant breast cancer cells.Flow cytometry(FCM)was utilized to measure the proportion of CD44+CD24-cells in MCF7/FulR.The correlation between HA synthesis genes and cell stemness was investigated in clinical ER+breast cancers from GEO data sets.Hyaluronidase(HAase)treatment was applied to remove the"HA coat",and RT-qPCR and Western blotting analysis were carried out to monitor changes in stemness-related molecules.CCK-8 assays,flow cytometry(FCM),and Hoechst 33258 staining were performed to determine changes in apoptosis and fulvestrant efficiency after HAase treatment.Results·IF results revealed that compared with MCF7 cells,the"HA coat"on the surface of MCF7/FulR cells was significantly thickened.IHC demonstrated markedly increased HA retention in fulvestrant-resistant mouse breast cancer tissues.ScRNA-seq and RNA-seq analyses indicated elevated expression of stemness-related genes and HA synthesis-associated genes in fulvestrant-resistant breast cancer cells.Correlation analysis revealed a positive association between HA synthesis and cancer stemness in ER+breast cancer.IF and RT-qPCR results demonstrated that removing the HA coating from the surface of MCF7/FulR cells led to a significant reduction in the expression of stemness-related molecules;concurrently,CCK-8 assays,FCM analysis,and Hoechst 33258 staining revealed that"HA coat"clearance reduced MCF7/FulR'tolerance to fulvestrant and increased apoptosis.Conclusion·Endocrine-resistant breast cancer cells develop an enriched"HA coat",which promotes stemness in fulvestrant-resistant tumors.Disruption of this HA coat through HAase treatment effectively reduces cell stemness,induces apoptosis,and re-sensitizes breast cancer cells to fulvestrant.

Objective To investigate the mechanism of action of the Astragalus-Chinese yam combination in treating cancer-related fatigue(CRF)in mice.Methods The active components and related targets of Astragalus-Chinese yam were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform.CRF-associated targets were identified using the GeneCards database.Intersecting targets were analyzed using the DAVID database for gene ontology and kyoto encyclopedia of genes and genomes enrichment analyses.A network diagram depicting"drug-active component-intersecting targets-disease"was constructed using Cytoscape software,and a protein-protein interaction network was created to identify the top five core target proteins based on degree values.Molecular docking simulations were performed using Autodock Vina software.Twenty-five mice were divided randomly into a blank group and a modeling group in a 1∶4 ratio.After successfully establishing the CRF model using Lewis lung cancer cells,mice in the modeling group were further divided into model,Chinese yam(0.2 g/kg),Astragalus(0.6 g/kg),and Astragalus-Chinese yam combination groups(0.3+0.1 g/kg)(n=5 mice per group).The treatments were administered by gavage twice daily for 14 consecutive days.Grip-strength and forced-swimming tests were conducted.The mice were then euthanized and tissues were collected.The gastrocnemius muscles were weighed and stained with hematoxylin and eosin to reveal the muscle fiber morphology.Results A total of 23 effective active components of Astragalus-Chinese yam were identified through network pharmacology analysis,with 199 intersecting drug-disease targets.These targets mainly participated in biological processes such as protein phosphorylation through cellular components(cytoplasm,membrane,nucleus)and performed molecular functions such as protein binding.A total of 155 signaling pathways,including pathway in cancer and the phosphatidylinositol 3-kinase-protein kinase B signaling pathway,were involved in CRF.The critical targets of Astragalus-Chinese yam for CRF included serine/threonine kinase,tumor necrosis factor,epidermal growth factor receptor,B-cell lymphoma 2,and caspase 3.The active components quercetin and diosgenin interacted with the highest number of targets and demonstrated binding energies＜-5.0 kJ/mol with the five core targets,indicating strong ligand-receptor binding affinity.Mice in the Chinese yam and Astragalus groups exhibited increased grip strength and prolonged swimming times compared with the model group.Gastrocnemius muscle volume and mass were increased,with well-organized muscle fibers and clear boundaries,and the effects were even more pronounced in the Astragalus-Chinese yam combination group.Conclusions Astragalus-Chinese yam treats CRF via a multi-target,multi-pathway approach,enhancing muscle strength and endurance in mice,improving gastrocnemius muscle volume and mass,and alleviating muscle atrophy,thereby mitigating the associated symptoms of CRF in mice.

Objective:To evaluate the effect of different psychosocial interventions on fertility concerns in cancer patients using network Meta-analysis.Methods:Randomized controlled trials or quasi-experimental studies on the effects of different psychosocial interventions on fertility concerns in cancer patients were electronically searched in China National Knowledge Infrastructure, Wanfang Data, VIP, China Biology Medicine disc, PubMed, Embase, Cochrane Library, CINAHL, Web of Science and PsycINFO. The search period was from database establishment to October 31, 2024. Two researchers independently conducted literature screening and data extraction. Conventional Meta-analysis of the included literature was performed using RevMan 5.4, and network Meta-analysis was performed using Stata 18.0.Results:A total of 10 studies involving 835 cancer patients and seven psychosocial interventions were included. Network Meta-analysis showed that there was a statistically significant difference in the intervention effect of fertility counseling ( MD=18.24, 95% CI: 2.85-33.62, P<0.05) and mental awareness training ( MD=17.97, 95% CI: 3.09-32.85, P<0.05) on fertility concerns in cancer patients as compared to routine nursing. The ranked probability plot showed that fertility counseling and mental awareness training had superior results. Conclusions:Fertility counseling has a superior effect on fertility concerns in cancer patients. Mental awareness training may be effective in improving fertility concerns in cancer patients, and further research is needed to validate the effectiveness of mindfulness-based stress reduction, cognitive behavioral therapy, dyadic coping interventions, and educational interventions in improving fertility concerns in cancer patients.

Pancreatic cancer(PC)is a highly malignant digestive system tumor with extremely high mortality and recurrence rates.While traditional surgical resection and chemotherapy remain the main treatment options,challenges such as high postoperative recurrence and poor prognosis persist.Therefore,exploring more effective comprehensive treatment strategies is crucial for improving patient survival and prognosis.This review systematically summarizes recent advances in systemic therapy for PC,with a focus on the application and efficacy of chemotherapy,targeted therapy,and immunotherapy.Additionally,it discusses the potential of neoadjuvant therapy,integrated traditional Chinese and Western medicine approaches,and conversion therapy in enhancing the effects of conventional chemotherapy.Studies have shown that targeted therapy can enhance antigen presentation and reduce side effects,while immune checkpoint inhibitors,cancer vaccines,and adoptive cell immunotherapy help mitigate tumor immune evasion and improve the tumor microenvironment.Despite continuous innovation in treatment approaches,clinical management of PC,particularly for advanced-stage patients,still faces significant challenges.Future research should focus on early diagnosis,precision medicine,and personalized treatment strategies to further improve cure rates and patient survival quality,providing more effective therapeutic options for clinical practice.