Based on the interleukin-17(IL-17) signaling pathway, this study explores the effect and mechanism of Bufei Decoction on Klebsiella pneumoniae pneumonia in rats. SD rats were randomly divided into the control group, model group, Bufei Decoction low-dose group(6.68 g·kg~(-1)·d~(-1)), Bufei Decoction high-dose group(13.36 g·kg~(-1)·d~(-1)), and dexamethasone group(1.04 mg·kg~(-1)·d~(-1)), with 10 rats in each group. A pneumonia model was established by tracheal drip injection of K. pneumoniae. After successful model establishment, the improvement in lung tissue damage was observed following drug administration. Core targets and signaling pathways were screened using transcriptomics techniques. Real-time fluorescence quantitative polymerase chain reaction was used to detect the mRNA expression of core targets interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and chemokine CXC ligand 6(CXCL6). Western blot was used to assess key proteins in the IL-17 signaling pathway, including interleukin-17A(IL-17A), nuclear transcription factor-κB activator 1(Act1), tumor necrosis factor receptor-associated factor 6(TRAF6), and downstream phosphorylated p38 mitogen-activated protein kinase(p-p38 MAPK), and phosphorylated nuclear factor-κB p65(p-NF-κB p65). Apoptosis of lung tissue cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL). The results showed that, compared with the control group, the model group exhibited significant pathological damage in lung tissue. The mRNA expression of IL-6, IL-1β, TNF-α, and CXCL6, as well as the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly increased, and the number of apoptotic cells was notably higher, indicating successful model establishment. Compared with the model group, both low-and high-dose groups of Bufei Decoction showed reduced pathological damage in lung tissue. The mRNA expression levels of IL-6, IL-1β, TNF-α, and CXCL6, and the protein levels of IL-17A, Act1, TRAF6, p-p38 MAPK/p38 MAPK, and p-NF-κB p65/NF-κB p65, were significantly decreased, with a significant reduction in apoptotic cells in the high-dose group. In conclusion, Bufei Decoction can effectively improve lung tissue damage and reduce inflammation in rats with K. pneumoniae. The mechanism may involve the regulation of the IL-17 signaling pathway and the reduction of apoptosis.
Animals ; Interleukin-17/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; Rats ; Male ; Klebsiella pneumoniae/physiology* ; Klebsiella Infections/immunology* ; Humans ; Lung/drug effects*

OBJECTIVE To investigate the mechanisms of adrenal dysfunction among adult offspring rats caused by prenatal ethanol exposure(PEE)aggravated by high-fat diet(HFD)and unpredictable chronic stress(UCS).METHODS Pregnant rats were randomly divided into the control group(saline,ig,once)and PEE group(4 g·kg-1,ig,once)from gestational day(GD)11 until delivery.At postnatal week 4(PW4),offspring rats from the control group and PEE group were randomly assigned to three sub-groups:the normal diet(ND)group,HFD group,and HFD-UCS group(n=20 per subgroup,at an equal male-to-female ratio).The rats in each group were given a corresponding diet until PW24.The HFD-UCS group received HFD until PW24,with additional UCS treatment initiated at PW21 and continued for 3 weeks.Serum adrenocorticotropic hormone(ACTH)levels were measured by radioimmunoassay,and corticosterone(CORT)levels were quantified via enzyme-linked immunosorbent assay(ELISA).Adrenal mRNA expressions of steroidogenic factor 1(Sf1),steroidogenic acute regulatory protein(Star),cyto-chrome P450 cholesterol side chain cleavage(P450scc),3β-hydroxysteroid dehydrogenase(3β-Hsd),steroid 21-hydroxylase(P450c21),steroid 11β-hydroxylase(P450c11),11β-hydroxysteroid dehydrogenase type 1(11β-Hsd1),11β-Hsd 2,mineralocorticoid receptor(Mr),glucocorticoid receptor(Gr),insulin-like growth factor 1(Igf1),IGF1 receptor(Igf1r),and serine/threonine kinase 1(Akt1)were determined using real-time quantitative PCR.Protein expressions of Akt1 and phosphorylated Akt1(p-Akt1)were analyzed via immunohistochemistry.RESULTS In male offspring,HFD/PEE significantly reduced serum ACTH and CORT levels,downregulated Star,P450scc,3β-Hsd and P450c11 mRNA,decreased 11β-Hsd1 mRNA expressions and 11β-Hsd1/11β-Hsd2 ratio,but increased Igf1,Igf1r mRNA,and p-Akt1 protein.Conversely,HFD-UCS/PEE elevated ACTH,CORT,P450scc,3β-Hsd and P450c11 mRNA,increased 11β-Hsd1 and 11β-Hsd1/11β-Hsd2 ratio while suppressing Igf1 mRNA,and p-Akt1 protein.In females,HFD/PEE decreased ACTH but upregulated Igf1,Akt1 mRNA,and p-Akt1 protein.HFD-UCS/PEE increased ACTH,CORT,Sf1,Star,P450scc and P450c11 mRNA,and 11β-Hsd1/11β-Hsd2 ratio,but reduced lgf1 and Igf1r mRNA.CONCLUSION HFD/UCS can aggravate PEE-induced adrenal dysfunction in adult offspring.The adrenal"GC-IGF1 axis"is an endocrine negative feedback one,and its decompensation may increase the susceptibility of a wide range of GC-related adult chronic diseases,such as diabetes.

Objective To explore the mechanism of electroacupuncture improving myocardial ischemia-reperfusion injury(MIRI),electroacupuncture PC6 Attenuates TRPV1 pathway in spinal cord C5-T6 dorsal root ganglion(DRG)on MIRI rats was observed.Methods After one week of experimental feeding,30 SD rats with normal electrocardiogram were randomly divided into sham-operated group and model group,PC6 group,non-meridian and non-acupuncture group,and PC6+capsaicin(TRPV1 receptor agonist)group,with 6 rats in each group.The MIRI model was prepared by ligation of the left anterior descending(LAD)coronary artery in the other groups.The next day after modeling,electroacupuncture of the"PC6"point in the EA group,electroacupuncture of the caudal"non-meridian non-points"in the the non-meridian non-acupuncture point group,and electroacupuncture of the"PC6"point after intraperitoneal injection of capsaicin in the PC6+capsaicin group,20 min/d for 7 days.ECG was used to record the changes of ST level and LF/HF ratio in rats.Evans blue-TTC double staining and HE staining was used to observe the myocardial infarction area and the changes of myocardial tissue morphology.ELISA was used to detect the levels of serum CK-MB and cTnI.Immunofluorescence staining was used to the phenomenon of sympathetic-sensory coupling with TH-CGRP positive labeling in the DRG of rats.qPCR was to detect the mRNA expression of TRPV1,TH,CGRP,SP,ERK and AKT in rat DRG.Results Compared with the sham-operated group,rats in the model group showed significant higher ST level and LF/HF ratio(both P<0.001),and IA/AAR ratio increased significantly(P<0.0001).Massive inflammatory cell infiltration,serum CK-MB,cTnI levels up-regulated significantly(both P<0.0001).The formation of TH-CGRP-labeled sympathetic budding phenomenon in the DRG and the TRPV1,TH,CGRP in the DRG,SP,ERK,and AKT mRNA expression levels increased significantly(both P<0.01).Compared with the model group,the ECG of the endograft group was significantly improved(both P<0.001).The IA/AAR ratio decreased significantly in PC6 group(P<0.001).The myocardial infarction area reduced significantly(P<0.0001).The levels of serum CK-MB and cTnI down-regulated significantly(both P<0.0001),and the phenomenon of sympathetic sprouting within DRG was not evident,and the DRG of the 6 corresponding mRNA expression decreased significantly(both P<0.01).Compared with the PC6 group,the effect of treatment was not obvious in the non-meridian and non-acupuncture group and PC6+capsaicin group,and the electrocardiogram,IA/AAR ratio,myocardial infarcted area,and serum CK-MB,and cTnI levels did not improve(both P<0.01),and a large number of sympathetic budding phenomena were seen in the DRG.The expression of the mRNA corresponding to the phase of 6 increased significantly(both P<0.01).Conculsion Electroacupuncture PC6 may reduce myocardial injury by inhibiting TRPV1 pathway-mediated sympatheticsprouting in dorsal root ganglia.

Aim To investigate the anti-Zika virus(ZIKV)mechanism of diterpenoid compound 9 from Euphorbia helioscopia in vitro.Methods The cytotox-icity of compound 9 was evaluated using the CCK-8 as-say.A ZIKV-infected Vero cell model was established,and the antiviral activity was assessed through RT-qPCR,plaque assay,Western blot,and immunofluores-cence.Furthermore,the mechanism of action was elu-cidated using multi-cell line validation,nanoparticle tracking analysis,cellular thermal shift assay,and mo-lecular docking.Results In Vero cells,compound 9 exhibited an EC50 of(3.95±0.15)μmol·L-1 and a CC50 of(272.12±8.56)μmol·L-1,demonstrating significantly higher antiviral efficacy than the positive control drug ribavirin(RBV).Its virus inactivation effect was time-dependent and could significantly re-duce viral load and plaque formation.Studies revealed that compound 9 altered the physicochemical properties of ZIKV particles,including reducing surface charge and increasing particle size distribution.Additionally,it significantly enhanced the thermal stability of the prM protein.Molecular docking analysis indicated that compound 9 formed a high-affinity interaction with the prM protein(binding energy:-38.52 kJ·mol-1)and stabilized its structure through hydrophobic interac-tions.Conclusion Compound 9 exerts in vitro anti-ZIKV activity by directly inactivating the virus,disrup-ting viral particle integrity,and targeting the prM pro-tein.

By reviewing modern research and integrating clinical practice， this paper elucidates the correlation between the traditional Chinese medicine theory of pathological accumulation from collateral obstruction and gap junction intercellular communication （GJIC）， as well as its theoretical connotation and clinical application in tumor prevention and treatment. Physiologically， gap junction and collateral channels share similarities in structural distribution， substance exchange and information transmission. Pathologically， metabolic coupling mediated by dysfunctional gap junction resembles collaterals stagnation， forming the basis of tumor pathogenesis. The establishment of heterotypic gap junction parallels collateral hyperactivity， contributing to tumor metastasis. The post-translational modifications （PTMs） disorder of connexins is similar to the deficiency of collaterals， serving as a driver of tumor progression. Clinically， tumor treatment should follow the pathomechanism of collateral obstruction leading to pathological accumulation. In the early stage， detoxifying and unblocking collaterals can restore intercellular communication and inhibit tumorigenesis； in the progressive stage， calming hyperactivity and suppressing aberrant collateral pathways can prevent metastasis by interrupting heterotypic gap junction formation； and in the terminal stage， supporting vital qi and modulating PTMs of connexins can help delay tumor progression.

Aim To investigate the anti-Zika virus(ZIKV)mechanism of diterpenoid compound 9 from Euphorbia helioscopia in vitro.Methods The cytotox-icity of compound 9 was evaluated using the CCK-8 as-say.A ZIKV-infected Vero cell model was established,and the antiviral activity was assessed through RT-qPCR,plaque assay,Western blot,and immunofluores-cence.Furthermore,the mechanism of action was elu-cidated using multi-cell line validation,nanoparticle tracking analysis,cellular thermal shift assay,and mo-lecular docking.Results In Vero cells,compound 9 exhibited an EC50 of(3.95±0.15)μmol·L-1 and a CC50 of(272.12±8.56)μmol·L-1,demonstrating significantly higher antiviral efficacy than the positive control drug ribavirin(RBV).Its virus inactivation effect was time-dependent and could significantly re-duce viral load and plaque formation.Studies revealed that compound 9 altered the physicochemical properties of ZIKV particles,including reducing surface charge and increasing particle size distribution.Additionally,it significantly enhanced the thermal stability of the prM protein.Molecular docking analysis indicated that compound 9 formed a high-affinity interaction with the prM protein(binding energy:-38.52 kJ·mol-1)and stabilized its structure through hydrophobic interac-tions.Conclusion Compound 9 exerts in vitro anti-ZIKV activity by directly inactivating the virus,disrup-ting viral particle integrity,and targeting the prM pro-tein.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

OBJECTIVE To investigate the mechanisms of adrenal dysfunction among adult offspring rats caused by prenatal ethanol exposure(PEE)aggravated by high-fat diet(HFD)and unpredictable chronic stress(UCS).METHODS Pregnant rats were randomly divided into the control group(saline,ig,once)and PEE group(4 g·kg-1,ig,once)from gestational day(GD)11 until delivery.At postnatal week 4(PW4),offspring rats from the control group and PEE group were randomly assigned to three sub-groups:the normal diet(ND)group,HFD group,and HFD-UCS group(n=20 per subgroup,at an equal male-to-female ratio).The rats in each group were given a corresponding diet until PW24.The HFD-UCS group received HFD until PW24,with additional UCS treatment initiated at PW21 and continued for 3 weeks.Serum adrenocorticotropic hormone(ACTH)levels were measured by radioimmunoassay,and corticosterone(CORT)levels were quantified via enzyme-linked immunosorbent assay(ELISA).Adrenal mRNA expressions of steroidogenic factor 1(Sf1),steroidogenic acute regulatory protein(Star),cyto-chrome P450 cholesterol side chain cleavage(P450scc),3β-hydroxysteroid dehydrogenase(3β-Hsd),steroid 21-hydroxylase(P450c21),steroid 11β-hydroxylase(P450c11),11β-hydroxysteroid dehydrogenase type 1(11β-Hsd1),11β-Hsd 2,mineralocorticoid receptor(Mr),glucocorticoid receptor(Gr),insulin-like growth factor 1(Igf1),IGF1 receptor(Igf1r),and serine/threonine kinase 1(Akt1)were determined using real-time quantitative PCR.Protein expressions of Akt1 and phosphorylated Akt1(p-Akt1)were analyzed via immunohistochemistry.RESULTS In male offspring,HFD/PEE significantly reduced serum ACTH and CORT levels,downregulated Star,P450scc,3β-Hsd and P450c11 mRNA,decreased 11β-Hsd1 mRNA expressions and 11β-Hsd1/11β-Hsd2 ratio,but increased Igf1,Igf1r mRNA,and p-Akt1 protein.Conversely,HFD-UCS/PEE elevated ACTH,CORT,P450scc,3β-Hsd and P450c11 mRNA,increased 11β-Hsd1 and 11β-Hsd1/11β-Hsd2 ratio while suppressing Igf1 mRNA,and p-Akt1 protein.In females,HFD/PEE decreased ACTH but upregulated Igf1,Akt1 mRNA,and p-Akt1 protein.HFD-UCS/PEE increased ACTH,CORT,Sf1,Star,P450scc and P450c11 mRNA,and 11β-Hsd1/11β-Hsd2 ratio,but reduced lgf1 and Igf1r mRNA.CONCLUSION HFD/UCS can aggravate PEE-induced adrenal dysfunction in adult offspring.The adrenal"GC-IGF1 axis"is an endocrine negative feedback one,and its decompensation may increase the susceptibility of a wide range of GC-related adult chronic diseases,such as diabetes.

Objective To explore the mechanism of electroacupuncture improving myocardial ischemia-reperfusion injury(MIRI),electroacupuncture PC6 Attenuates TRPV1 pathway in spinal cord C5-T6 dorsal root ganglion(DRG)on MIRI rats was observed.Methods After one week of experimental feeding,30 SD rats with normal electrocardiogram were randomly divided into sham-operated group and model group,PC6 group,non-meridian and non-acupuncture group,and PC6+capsaicin(TRPV1 receptor agonist)group,with 6 rats in each group.The MIRI model was prepared by ligation of the left anterior descending(LAD)coronary artery in the other groups.The next day after modeling,electroacupuncture of the"PC6"point in the EA group,electroacupuncture of the caudal"non-meridian non-points"in the the non-meridian non-acupuncture point group,and electroacupuncture of the"PC6"point after intraperitoneal injection of capsaicin in the PC6+capsaicin group,20 min/d for 7 days.ECG was used to record the changes of ST level and LF/HF ratio in rats.Evans blue-TTC double staining and HE staining was used to observe the myocardial infarction area and the changes of myocardial tissue morphology.ELISA was used to detect the levels of serum CK-MB and cTnI.Immunofluorescence staining was used to the phenomenon of sympathetic-sensory coupling with TH-CGRP positive labeling in the DRG of rats.qPCR was to detect the mRNA expression of TRPV1,TH,CGRP,SP,ERK and AKT in rat DRG.Results Compared with the sham-operated group,rats in the model group showed significant higher ST level and LF/HF ratio(both P<0.001),and IA/AAR ratio increased significantly(P<0.0001).Massive inflammatory cell infiltration,serum CK-MB,cTnI levels up-regulated significantly(both P<0.0001).The formation of TH-CGRP-labeled sympathetic budding phenomenon in the DRG and the TRPV1,TH,CGRP in the DRG,SP,ERK,and AKT mRNA expression levels increased significantly(both P<0.01).Compared with the model group,the ECG of the endograft group was significantly improved(both P<0.001).The IA/AAR ratio decreased significantly in PC6 group(P<0.001).The myocardial infarction area reduced significantly(P<0.0001).The levels of serum CK-MB and cTnI down-regulated significantly(both P<0.0001),and the phenomenon of sympathetic sprouting within DRG was not evident,and the DRG of the 6 corresponding mRNA expression decreased significantly(both P<0.01).Compared with the PC6 group,the effect of treatment was not obvious in the non-meridian and non-acupuncture group and PC6+capsaicin group,and the electrocardiogram,IA/AAR ratio,myocardial infarcted area,and serum CK-MB,and cTnI levels did not improve(both P<0.01),and a large number of sympathetic budding phenomena were seen in the DRG.The expression of the mRNA corresponding to the phase of 6 increased significantly(both P<0.01).Conculsion Electroacupuncture PC6 may reduce myocardial injury by inhibiting TRPV1 pathway-mediated sympatheticsprouting in dorsal root ganglia.