ObjectiveTo investigate the effects of Huangqi Jianzhongtang （HQJZ） on macrophage polarization and fat consumption in cancer cachexia （CC） mice. MethodsUltra-performance liquid chromatography-quadrupole/electrostatic field Orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap HRMS） was used to control the quality of HQJZ. （1） In vitro experiment： HQJZ-containing serum was prepared， and the optimal concentration was determined by cytotoxicity assay. Mouse monocyte-derived macrophages （RAW264.7） were cultured and randomly divided into six groups， including a blank group， a classically activated macrophages （M1） group， an alternatively activated macrophages （M2） group， a HQJZ + blank group， a HQJZ+M1 group， and a HQJZ + M2 group. The relative expression of macrophage marker genes CD86， inducible nitric oxide synthase （iNOS）， CD206， and arginase-1 （Arg1） was detected by real-time quantitative polymerase chain reaction （Real-time PCR ）. （2） In vivo experiment： Thirty-two BALB/c mice were randomly divided into a control group， a model group， a medroxyprogesterone acetate （MPA） group， and a HQJZ group. Except for the control group， the other mice were injected with CT-26 colon cancer cells to establish a CC model. Mice in the MPA and HQJZ groups were given MPA （0.13 g·kg^-1·d^-1） or HQJZ （13.13 g·kg^-1·d^-1） by gavage， respectively， while mice in the control and model groups were given an equal volume of saline by gavage， with interventions continued for 10 d. Real-time PCR was used to detect the expression of macrophage markers （iNOS， Arg1， CD86， CD206） and fat browning-related genes uncoupling protein 1 （UCP1） and peroxisome proliferator-activated receptor γ （PPARγ） in epididymal adipose tissue. Western blot （WB） was used to detect protein expression levels of UCP1 and PPARγ. Micro-computed tomography （micro-CT） was used to measure residual fat volume， and hematoxylin-eosin （HE） staining was used to assess fat browning and calculate pathological scores. ResultsIn vitro， the dominant effective concentration of HQJZ-containing serum was 12.5%. Real-time PCR results showed that， compared with the blank group， Arg1 expression decreased in the HQJZ+blank group （P<0.05）， CD206 showed a downward trend without statistical significance， while iNOS and CD86 expression were significantly increased （P<0.05）. Compared with the M1 group， Arg1 and CD206 expression decreased in the HQJZ+M1 group （P<0.05）. Compared with the M2 group， CD206 expression decreased in the HQJZ+M2 group （P<0.05）， CD86 expression increased significantly （P<0.01）. In vivo， Real-time PCR results showed that， compared with the control group， CD86 and CD206 expression levels were significantly increased in the model group （P<0.01）. Compared with the model group， CD206 expression in the MPA group was significantly decreased （P<0.01）. In the HQJZ group， CD206 was significantly decreased （P<0.01）. WB results showed that， compared with the model group， protein expression of UCP1 and PPARγ was significantly reduced in the HQJZ group （P<0.05， P<0.01）. micro-CT results showed that the total white fat volume in the HQJZ group was greater than that in the model group （P<0.05）. HE staining results showed that pathological scores in the HQJZ group were lower than those in the model group （P<0.05）. ConclusionHQJZ may inhibit white adipose tissue browning by promoting macrophage M1 polarization and suppressing M2 polarization， thereby delaying fat consumption in CC mice.

Sepsis is a potentially fatal infectious disease that easily causes shock and numerous organ failures. The kidney is one of the most susceptible to injury. Early intervention and renal protection significantly minimize patient mortality. Oligomeric proanthocyanidin (OPC), a naturally occurring plant compound, has a high potential for renal protection. This study was aimed at exploring the potential renoprotective role of OPC in sepsis-related renal tubular injury. C57/B6 mice were intraperitoneally injected with lipopolysaccharide (LPS) to simulate sepsis-related acute kidney injury in vivo. Renal function and pathology were assessed. RNA sequencing examined OPC mechanisms against LPS-induced renal injury. Oxidative stress indicators and inflammatory cytokines in blood serum and renal tissues were evaluated. In vitro, MTT assays assess cell viability. Apoptosis cells were detected using Hoechst 33342 and propidium iodide staining. Western blot assessed PI3K/AKT and NFκB signaling pathway proteins. OPC reduced LPS-induced renal tubular injury, improved renal functions and pathological changes, restored glutathione content, superoxide dismutase activity, and catalase activity, inhibited malondialdehyde overproduction, and suppressed LPS-induced overproduction of pro-inflammatory cytokines and the decline of anti-inflammatory cytokines. OPC attenuated LPS-induced cell morphological injury, reduced cell viability loss, and recovered the changes in proteins involved in PI3K/AKT and NFκB signaling pathways in MTEC cells. OPC protects against LPSinduced renal tubular injury by counteracting oxidative stress, inhibiting inflammatory responses, activating the PI3K/AKT signaling pathway, and inhibiting the NFκB signaling pathway. It may provide a viable solution to lessen renal injury in patients with sepsis.

Sepsis is a potentially fatal infectious disease that easily causes shock and numerous organ failures. The kidney is one of the most susceptible to injury. Early intervention and renal protection significantly minimize patient mortality. Oligomeric proanthocyanidin (OPC), a naturally occurring plant compound, has a high potential for renal protection. This study was aimed at exploring the potential renoprotective role of OPC in sepsis-related renal tubular injury. C57/B6 mice were intraperitoneally injected with lipopolysaccharide (LPS) to simulate sepsis-related acute kidney injury in vivo. Renal function and pathology were assessed. RNA sequencing examined OPC mechanisms against LPS-induced renal injury. Oxidative stress indicators and inflammatory cytokines in blood serum and renal tissues were evaluated. In vitro, MTT assays assess cell viability. Apoptosis cells were detected using Hoechst 33342 and propidium iodide staining. Western blot assessed PI3K/AKT and NFκB signaling pathway proteins. OPC reduced LPS-induced renal tubular injury, improved renal functions and pathological changes, restored glutathione content, superoxide dismutase activity, and catalase activity, inhibited malondialdehyde overproduction, and suppressed LPS-induced overproduction of pro-inflammatory cytokines and the decline of anti-inflammatory cytokines. OPC attenuated LPS-induced cell morphological injury, reduced cell viability loss, and recovered the changes in proteins involved in PI3K/AKT and NFκB signaling pathways in MTEC cells. OPC protects against LPSinduced renal tubular injury by counteracting oxidative stress, inhibiting inflammatory responses, activating the PI3K/AKT signaling pathway, and inhibiting the NFκB signaling pathway. It may provide a viable solution to lessen renal injury in patients with sepsis.

Sepsis is a potentially fatal infectious disease that easily causes shock and numerous organ failures. The kidney is one of the most susceptible to injury. Early intervention and renal protection significantly minimize patient mortality. Oligomeric proanthocyanidin (OPC), a naturally occurring plant compound, has a high potential for renal protection. This study was aimed at exploring the potential renoprotective role of OPC in sepsis-related renal tubular injury. C57/B6 mice were intraperitoneally injected with lipopolysaccharide (LPS) to simulate sepsis-related acute kidney injury in vivo. Renal function and pathology were assessed. RNA sequencing examined OPC mechanisms against LPS-induced renal injury. Oxidative stress indicators and inflammatory cytokines in blood serum and renal tissues were evaluated. In vitro, MTT assays assess cell viability. Apoptosis cells were detected using Hoechst 33342 and propidium iodide staining. Western blot assessed PI3K/AKT and NFκB signaling pathway proteins. OPC reduced LPS-induced renal tubular injury, improved renal functions and pathological changes, restored glutathione content, superoxide dismutase activity, and catalase activity, inhibited malondialdehyde overproduction, and suppressed LPS-induced overproduction of pro-inflammatory cytokines and the decline of anti-inflammatory cytokines. OPC attenuated LPS-induced cell morphological injury, reduced cell viability loss, and recovered the changes in proteins involved in PI3K/AKT and NFκB signaling pathways in MTEC cells. OPC protects against LPSinduced renal tubular injury by counteracting oxidative stress, inhibiting inflammatory responses, activating the PI3K/AKT signaling pathway, and inhibiting the NFκB signaling pathway. It may provide a viable solution to lessen renal injury in patients with sepsis.

Sepsis is a potentially fatal infectious disease that easily causes shock and numerous organ failures. The kidney is one of the most susceptible to injury. Early intervention and renal protection significantly minimize patient mortality. Oligomeric proanthocyanidin (OPC), a naturally occurring plant compound, has a high potential for renal protection. This study was aimed at exploring the potential renoprotective role of OPC in sepsis-related renal tubular injury. C57/B6 mice were intraperitoneally injected with lipopolysaccharide (LPS) to simulate sepsis-related acute kidney injury in vivo. Renal function and pathology were assessed. RNA sequencing examined OPC mechanisms against LPS-induced renal injury. Oxidative stress indicators and inflammatory cytokines in blood serum and renal tissues were evaluated. In vitro, MTT assays assess cell viability. Apoptosis cells were detected using Hoechst 33342 and propidium iodide staining. Western blot assessed PI3K/AKT and NFκB signaling pathway proteins. OPC reduced LPS-induced renal tubular injury, improved renal functions and pathological changes, restored glutathione content, superoxide dismutase activity, and catalase activity, inhibited malondialdehyde overproduction, and suppressed LPS-induced overproduction of pro-inflammatory cytokines and the decline of anti-inflammatory cytokines. OPC attenuated LPS-induced cell morphological injury, reduced cell viability loss, and recovered the changes in proteins involved in PI3K/AKT and NFκB signaling pathways in MTEC cells. OPC protects against LPSinduced renal tubular injury by counteracting oxidative stress, inhibiting inflammatory responses, activating the PI3K/AKT signaling pathway, and inhibiting the NFκB signaling pathway. It may provide a viable solution to lessen renal injury in patients with sepsis.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

The coinfection of respiratory viruses and bacteria is a major cause of morbidity and mortality worldwide, despite the development of vaccines and powerful antibiotics. As a macromolecule that is difficult to absorb in the gastrointestinal tract, a homogeneous polysaccharide from Houttuynia cordata (HCPM) has been reported to exhibit anti-complement properties and alleviate influenza A virus (H1N1)-induced lung injury; however, the effects of HCPM without in vitro antiviral and antibacterial activities on more complicated pulmonary diseases resulting from viral-bacterial coinfection remains unclear. This study established a representative coinfection murine pneumonia model infected with H1N1 (0.2 LD₅₀) and methicillin-resistant Staphylococcus aureus (MRSA, 10⁷ CFU). HCPM significantly improved survival rate and weight loss, and ameliorated gut-lung damage and inflammatory cytokine production. Interestingly, the therapeutic effect of HCPM on intestinal damage preceded that in the lungs. Mechanistically, HCPM inhibited the overactivation of the intestinal complement (C3a and C5a) and suppressed the activation of the NLR family pyrin domain-containing 3 (NLRP3) pathway, which contributes to the regulation of the Treg/Th17 cell balance in the gut-lung axis. The results indicate the beneficial effects of an anti-complement polysaccharide against viral-bacterial coinfection pneumonia by modulating crosstalk between multiple immune regulatory networks.

Image 1.

Heatstroke, a life-threatening illness, poses a significant risk to human health, particularly in high-temperature and high-humidity environments. Timely and effective on-site management is critical for improving patient survival and prognosis. Rapid recognition, rapid assessment, and rapid cooling are the cornerstones of pre-hospital care. However, the absence of a standardized protocol for pre-hospital management of heatstroke has impeded the efficacy of treatment. This consensus, initiated by the Expert Group on Heatstroke Prevention of the People's Liberation Army, signifies a collaborative endeavor involving emergency medical personnel, nurses, and administrators from pre-hospital care, emergency departments, and intensive care units in both military and civilian domains. By systematically reviewing evidence-based medicine and clinical expertise in heatstroke prevention, on-site and in-transit care, as well as early treatment in emergency settings, the group has formulated the Expert consensus on pre-hospital emergency management of heatstroke (2024) after extensive discussions and iterative recommendations, which serve as a scientific and standardized framework for pre-hospital heatstroke emergency care. The consensus underscores the pivotal role of enhancing public awareness regarding heatstroke prevention and augmenting the rates of rapid recognition and rapid cooling for effective on-site heatstroke management. In high-risk industries, regions, or seasons for heatstroke, developing scientifically sound plans and conducting practical training can provide effective safety measures. Emergency personnel should undergo specialized training and assessments in knowledge and skills, ambulances should be equipped with effective cooling devices, and hospitals must maintain comprehensive emergency response capabilities. It is recommended to establish a regional heatstroke treatment network to optimize the allocation of emergency resources and streamline processes, thereby improving treatment outcomes and response times.
Heat Stroke/prevention & control* ; Humans ; Emergency Medical Services ; Consensus

Objective To explore the effects of sigma-1 receptor(Sig-1R)on brain function in rats after cardiopulmo-nary resuscitation and its protective role in brain injury.Methods Rats were randomly assigned to four groups with 20 in each:sham-operated control(sham group),6-hour post-resuscitation(PR 6 h group),12-hour post-resuscitation(PR 12 h group)and 24-hour post-resuscitation(PR 24 h group).In the latter three groups,cardiac arrest was induced by as-phyxiation,and cardiopulmonary resuscitation was performed 6 minutes after cardiac arrest.The rats were scored for neu-rological deficits at 6,12 and 24 hrs after resuscitation,respectively;after that,the rats were executed,and the expres-sion of Sig-1R protein,mitochondrial function index,and endoplasmic reticulum stress index apoptosis index were detec-ted by Western blot and immunohistochemistry.The correlation between Sig-1R and mitochondrial,endoplasmic reticulum stress and apoptosis indexes was evaluated.Results Compared with the sham-operated group,the rats in test group showed a gradual decrease in neurological deficit scores,Sig-1R protein expression,brain tissue adenosine triphos-phate(ATP)concentration and mitochondrial membrane potential(MMP)levels at 6,12,and 24 hrs of PR(P＜0.05);CHOP protein,activated cleaved caspase-12 and cleaved caspase-3 protein expression were consistently elevated(P＜0.05).In addition,Sig-1R was negatively correlated with brain tissue endoplasmic reticulum stress and apoptosis(P＜0.05)but positively correlated with mitochondrial membrane potential level(P＜0.05).Conclusions Sig-1R ex-pression in rat brain tissue correlates with brain injury after cardiopulmonary resuscitation and potential mechanism seems to be neuronal protection through modulating mitochondrial function and endoplasmic reticulum stress.