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.

ObjectiveTo investigate the therapeutic mechanism of Danhe granules in treating mixed hyperlipidemia based on network pharmacology， as well as animal and cell experiments. MethodsThe active compounds and targets of Danhe granules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）. Related targets for mixed hyperlipidemia were obtained from the GeneCards database. The intersecting targets were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. A high-fat model was established in human hepatocellular carcinoma cells （HepG2） induced by palmitic acid （PA）， followed by intervention with Danhe granules to assess intracellular lipid accumulation and oxidative stress levels. A mixed hyperlipidemia rat model was also established and divided into low-， medium-， and high-dose Danhe granules groups （1.134， 2.268， and 4.536 g·kg^-1， respectively）， as well as a positive control group treated with pravastatin sodium （4.020 mg·kg^-1）. After eight weeks of intervention， serum lipid levels， inflammatory factors， oxidative stress indices， and the expression of key hepatic lipid metabolism-related proteins were determined. ResultsNetwork pharmacology identified 93 intersecting targets between Danhe granules and mixed hyperlipidemia， with peroxisome proliferator-activated receptor gamma （PPARG）， peroxisome proliferator-activated receptor alpha （PPARA）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and IL-1B among the key nodes. The PPAR signaling pathway， AGE/RAGE signaling pathway， lipid metabolism， atherosclerosis and non-alcoholic fatty liver disease （NAFLD） were among the most significantly enriched pathways. Cellular experiments demonstrated that Danhe granules significantly reduced reactive oxygen species （ROS） and malondialdehyde （MDA） levels while increasing catalase （CAT） activity （P<0.05）， thereby alleviating intracellular lipid accumulation and triglyceride （TG） content in HepG2. In animal experiments， Danhe granules markedly decreased serum total cholesterol （TC）， TG， and low-density lipoprotein cholesterol （LDL-C） levels （P<0.05）， reduced hepatic MDA levels， and elevated superoxide dismutase （SOD） and CAT levels. Histological analysis showed alleviation of hepatic steatosis， upregulation of hepatic PPARA and lipoprotein lipase （LPL） expressions， and downregulation of sterol regulatory element-binding protein 1 （SREBP1） expression （P<0.05， P<0.01）. ConclusionDanhe granules improve lipid metabolism disorders in mixed hyperlipidemia by reducing MDA levels， enhancing SOD and CAT activities， scavenging excessive ROS， inhibiting oxidative stress， and mitigating liver injury. The underlying mechanism may involve the upregulation of PPARA and LPL and the suppression of SREBP1 expression.

ObjectiveTo investigate the therapeutic mechanism of Danhe granules in treating mixed hyperlipidemia based on network pharmacology， as well as animal and cell experiments. MethodsThe active compounds and targets of Danhe granules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）. Related targets for mixed hyperlipidemia were obtained from the GeneCards database. The intersecting targets were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. A high-fat model was established in human hepatocellular carcinoma cells （HepG2） induced by palmitic acid （PA）， followed by intervention with Danhe granules to assess intracellular lipid accumulation and oxidative stress levels. A mixed hyperlipidemia rat model was also established and divided into low-， medium-， and high-dose Danhe granules groups （1.134， 2.268， and 4.536 g·kg^-1， respectively）， as well as a positive control group treated with pravastatin sodium （4.020 mg·kg^-1）. After eight weeks of intervention， serum lipid levels， inflammatory factors， oxidative stress indices， and the expression of key hepatic lipid metabolism-related proteins were determined. ResultsNetwork pharmacology identified 93 intersecting targets between Danhe granules and mixed hyperlipidemia， with peroxisome proliferator-activated receptor gamma （PPARG）， peroxisome proliferator-activated receptor alpha （PPARA）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and IL-1B among the key nodes. The PPAR signaling pathway， AGE/RAGE signaling pathway， lipid metabolism， atherosclerosis and non-alcoholic fatty liver disease （NAFLD） were among the most significantly enriched pathways. Cellular experiments demonstrated that Danhe granules significantly reduced reactive oxygen species （ROS） and malondialdehyde （MDA） levels while increasing catalase （CAT） activity （P<0.05）， thereby alleviating intracellular lipid accumulation and triglyceride （TG） content in HepG2. In animal experiments， Danhe granules markedly decreased serum total cholesterol （TC）， TG， and low-density lipoprotein cholesterol （LDL-C） levels （P<0.05）， reduced hepatic MDA levels， and elevated superoxide dismutase （SOD） and CAT levels. Histological analysis showed alleviation of hepatic steatosis， upregulation of hepatic PPARA and lipoprotein lipase （LPL） expressions， and downregulation of sterol regulatory element-binding protein 1 （SREBP1） expression （P<0.05， P<0.01）. ConclusionDanhe granules improve lipid metabolism disorders in mixed hyperlipidemia by reducing MDA levels， enhancing SOD and CAT activities， scavenging excessive ROS， inhibiting oxidative stress， and mitigating liver injury. The underlying mechanism may involve the upregulation of PPARA and LPL and the suppression of SREBP1 expression.

AIM:To observe the effects of Huangqi-Danggui mixture(HQDG)on the pyroptosis of brain tis-sues in rats with middle cerebral artery occlusion/reperfusion(MCAO/R),and to explore the mechanism of neuroprotec-tion provided by HQDG.METHODS:Sixty-four SD rats were randomly divided into 4 groups:sham group,model group,HQDG group,and Xuesaitong(XST)group.The infarct volume of brain tissues was observed by 2,3,5-triphenyl-tetrazolium chloride staining,while hematoxylin-eosin staining was used to observe the pathological changes of brain tis-sues.Immunofluorescence was employed to assess the expression of nucleotide-binding oligomerization domain-like recep-tor protein 3(NLRP3),cleaved caspase-1 and gasdermin D(GSDMD)in the ischemic penumbra of brain tissues.The se-rum levels of interleukin-1β(IL-1β)and IL-18 were measured using ELISA.Western blot was used to detect NLRP3,cleaved caspase-1,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),IL-1β and IL-18 in brain tissues.RESULTS:Compared with sham group,the neurological deficit scores of the rats in model group were significantly increased(P<0.01),while those in HQDG and XST groups were significantly reduced compared with model group(P<0.01).The cerebral infarct volume ratio was significantly reduced in HQDG and XST groups compared with model group(P<0.01).The pathological damage of brain tissue in HQDG and XST groups was significantly reduced compared with model group.The positive rates of NLRP3,cleaved caspase-1 and GSDMD in the ischemic penumbra of brain tissues were significantly decreased in HQDG group compared with model group(P<0.01).The expression of pyrop-tosis-related proteins,NLRP3,cleaved caspase-1 and ASC,in the ischemic penumbra of brain tissues was significantly el-evated in model group compared with sham group(P<0.01),and significantly decreased in HQDG group compared with model group(P<0.01).The serum levels of IL-1β and IL-18 were significantly increased in model group compared with sham group(P<0.01),and significantly reduced in HQDG group compared with model group(P<0.01).CONCLU-SION:The HQDG effectively attenuates brain tissue injury in rats with MCAO/R,and its mechanism may be related to the inhibition of neural cell pyroptosis.

AIM:To investigate how the stearoyl-CoA desaturase-1(SCD1)inhibitor CAY-10566 induc-es ferroptosis in oral squamous cell carcinoma(OS-CC)cells and enhances their sensitivity to cisplatin,with preliminary exploration of the underlying mo-lecular mechanisms.METHODS:Bioinformatics analysis and clinical specimens were used to evalu-ate SCD1 expression in OSCC tissues.OSCC cell lines(Cal27 and HSC3)were treated with CAY-10566,cis-platin,the ferroptosis inhibitor Ferrostatin-1(Fer-1),or their combinations.Cell viability was assessed using the CCK-8 assay,while reactive oxygen spe-cies(ROS)and lipid ROS levels were measured by flow cytometry.Malondialdehyde(MDA)and re-duced glutathione(GSH)levels were quantified us-ing commercial assay kits.Western blotting was performed to analyze the protein expression of glu-tathione peroxidase 4(GPX4),mechanistic target of rapamycin(mTOR),mature sterol regulatory ele-ment-binding protein 1(m-SREBP1),SCD1,and heme oxygenase 1(HMOX1).RESULTS:SCD1 was significantly overexpressed in OSCC tissues(P＜0.01).Combined treatment with CAY-10566 and cis-platin markedly reduced OSCC cell viability(P＜0.01)and increased lipid peroxidation(P＜0.001),while suppressing GPX4 expression-effects that were re-versed by Fer-1(P＜0.001).CAY-10566 upregulated HMOX1 expression and inhibited mTOR,m-SREBP1,and SCD1 protein levels(P＜0.001).CONCLUSION:CAY-10566 promotes ferroptosis and cisplatin sensi-tivity in OSCC cells,potentially through HMOX1 up-regulation and suppression of the mTOR/SREBP1/SCD1 axis.

Syringa pinnatifolia, belonging to the family Oleaceae, is a species endemic to China. It is predominantly distributed in the Helan Mountains region of Inner Mongolia and Ningxia of China. The peeled roots, stems, and thick branches have been used as a distinctive Mongolian medicinal material known as "Shan-chen-xiang", which has effects such as suppressing "khii", clearing heat, and relieving pain and is employed for the treatment of cardiovascular and pulmonary diseases and joint pain. Over the past five years, significant increase was achieved in research on chemical constituents and pharmacological effects. There were a total of 130 new constituents reported, covering sesquiterpenoids, lignans, and alkaloids. Its effects of anti-myocardial ischemia, anti-cerebral ischemia/reperfusion, sedation, and analgesia were revealed, and the mechanisms of agarwood formation were also investigated. To better understand its medical value and potential of clinical application, this review updates the research progress in recent five years focusing on the chemical constituents and pharmacological effects of S. pinnatifolia, providing reference for subsequent research on active ingredient and support for its innovative application in modern medicine system.
Medicine, Mongolian Traditional ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Syringa/chemistry*

Bawei Chenxiang Powder(BCP), first documented in the Tibetan medical work Four Medical Classics, has been widely applied in clinical practices in Tibetan and Mongolian medicines since its development. It has the effect of clearing the heart heat, calming the mind, and inducing resuscitation. On the basis of BCP, multiple types of formulae have been developed, such as Bawei Yiheyi Chenxiang Powder, Bawei Rang Chenxiang Powder, and Bawei Pingchuan Chenxiang Powder, which are widely used for treating cardiovascular and respiratory diseases. Current pharmacological research has revealed the pharmacological effects of BCP and its related formulae against myocardial ischemia, cerebral ischemia, renal ischemia, and anti-hypoxia. BCP and its related formulae introduced more treatment options for related clinical diseases and provided insights for fully comprehending the essence and pharmacological components of the formulae. This paper systematically reviewed the clinical and pharmacological research on BCP and its related formulae, analyzing the formulation principles and potential key flavors and active ingredients. This lays a fundamental scientific basis for the clinical use, quality evaluation, and subsequent development and application of BCP and its related formulae, providing references for studying traditional Chinese medicine formulae in a thorough and systematic manner.
Drugs, Chinese Herbal/chemistry* ; Humans ; Powders/chemistry* ; Animals ; Medicine, Chinese Traditional

The medicinal materials of Bawei Chenxiang Pills(BCPs) were extracted via three methods: reflux extraction by water, reflux extraction by 70% ethanol, and extraction by pure water following reflux extraction by 70% ethanol, yielding three extracts of ST, CT, and CST. The efficacy of ST(760 mg·kg~(-1)), CT(620 mg·kg~(-1)), and CST(1 040 mg·kg~(-1)) were evaluated by acute myocardial ischemia(AMI) and p-chlorophenylalanine(PCPA)-induced insomnia in mice, respectively. Western blot was further utilized to investigate their hypnosis mechanisms. The main chemical components of different extracts were identified by the UPLC-Q-Exactive-MS technique. The results showed that CT and CST significantly increased the ejection fraction(EF) and fractional shortening(FS) of myocardial infarction mice, reduced left ventricular internal dimension at end-diastole(LVIDd) and left ventricular internal dimension at end-systole(LVIDs). In contrast, ST did not exhibit significant effects on these parameters. In the insomnia model, CT significantly reduced sleep latency and prolonged sleep duration, whereas ST only prolonged sleep duration without shortening sleep latency. CST showed no significant effects on either sleep latency or sleep duration. Additionally, both CT and ST upregulated glutamic acid decarboxylase 67(GAD67) protein expression in brain tissue. A total of 15 main chemical components were identified from CT, including 2-(2-phenylethyl) chromone and 6-methoxy-2-(2-phenylethyl) chromone. Six chemical components including chebulidic acid were identified from ST. The results suggested that chromones and terpenes were potential anti-myocardial ischemia drugs of BCPs, and tannin and phenolic acids were potential hypnosis drugs. This study enriches the pharmacological and chemical research of BCPs, providing a basis and reference for their secondary development, quality standard improvement, and clinical application.
Animals ; Drugs, Chinese Herbal/isolation & purification* ; Mice ; Male ; Sleep Initiation and Maintenance Disorders/physiopathology* ; Humans ; Myocardial Infarction/drug therapy* ; Myocardial Ischemia/drug therapy*

AIM:To observe the effects of Huangqi-Danggui mixture(HQDG)on the pyroptosis of brain tis-sues in rats with middle cerebral artery occlusion/reperfusion(MCAO/R),and to explore the mechanism of neuroprotec-tion provided by HQDG.METHODS:Sixty-four SD rats were randomly divided into 4 groups:sham group,model group,HQDG group,and Xuesaitong(XST)group.The infarct volume of brain tissues was observed by 2,3,5-triphenyl-tetrazolium chloride staining,while hematoxylin-eosin staining was used to observe the pathological changes of brain tis-sues.Immunofluorescence was employed to assess the expression of nucleotide-binding oligomerization domain-like recep-tor protein 3(NLRP3),cleaved caspase-1 and gasdermin D(GSDMD)in the ischemic penumbra of brain tissues.The se-rum levels of interleukin-1β(IL-1β)and IL-18 were measured using ELISA.Western blot was used to detect NLRP3,cleaved caspase-1,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),IL-1β and IL-18 in brain tissues.RESULTS:Compared with sham group,the neurological deficit scores of the rats in model group were significantly increased(P<0.01),while those in HQDG and XST groups were significantly reduced compared with model group(P<0.01).The cerebral infarct volume ratio was significantly reduced in HQDG and XST groups compared with model group(P<0.01).The pathological damage of brain tissue in HQDG and XST groups was significantly reduced compared with model group.The positive rates of NLRP3,cleaved caspase-1 and GSDMD in the ischemic penumbra of brain tissues were significantly decreased in HQDG group compared with model group(P<0.01).The expression of pyrop-tosis-related proteins,NLRP3,cleaved caspase-1 and ASC,in the ischemic penumbra of brain tissues was significantly el-evated in model group compared with sham group(P<0.01),and significantly decreased in HQDG group compared with model group(P<0.01).The serum levels of IL-1β and IL-18 were significantly increased in model group compared with sham group(P<0.01),and significantly reduced in HQDG group compared with model group(P<0.01).CONCLU-SION:The HQDG effectively attenuates brain tissue injury in rats with MCAO/R,and its mechanism may be related to the inhibition of neural cell pyroptosis.

AIM:To investigate how the stearoyl-CoA desaturase-1(SCD1)inhibitor CAY-10566 induc-es ferroptosis in oral squamous cell carcinoma(OS-CC)cells and enhances their sensitivity to cisplatin,with preliminary exploration of the underlying mo-lecular mechanisms.METHODS:Bioinformatics analysis and clinical specimens were used to evalu-ate SCD1 expression in OSCC tissues.OSCC cell lines(Cal27 and HSC3)were treated with CAY-10566,cis-platin,the ferroptosis inhibitor Ferrostatin-1(Fer-1),or their combinations.Cell viability was assessed using the CCK-8 assay,while reactive oxygen spe-cies(ROS)and lipid ROS levels were measured by flow cytometry.Malondialdehyde(MDA)and re-duced glutathione(GSH)levels were quantified us-ing commercial assay kits.Western blotting was performed to analyze the protein expression of glu-tathione peroxidase 4(GPX4),mechanistic target of rapamycin(mTOR),mature sterol regulatory ele-ment-binding protein 1(m-SREBP1),SCD1,and heme oxygenase 1(HMOX1).RESULTS:SCD1 was significantly overexpressed in OSCC tissues(P＜0.01).Combined treatment with CAY-10566 and cis-platin markedly reduced OSCC cell viability(P＜0.01)and increased lipid peroxidation(P＜0.001),while suppressing GPX4 expression-effects that were re-versed by Fer-1(P＜0.001).CAY-10566 upregulated HMOX1 expression and inhibited mTOR,m-SREBP1,and SCD1 protein levels(P＜0.001).CONCLUSION:CAY-10566 promotes ferroptosis and cisplatin sensi-tivity in OSCC cells,potentially through HMOX1 up-regulation and suppression of the mTOR/SREBP1/SCD1 axis.