Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Objective:To investigate the effects of Xingnao Yisui Decoction on the behaviour of vascular dementia (VaD) rats and the apoptosis of neurons in the CA1 region of the hippocampus; To explore its mechanism of action.Methods:Totally 60 adult SD rats with similar levels of cognitive function were selected and divided into Xingnao Yisui Decoction high-, medium- and low-dosage groups, donepezil group, model group and sham-operation group according to the random number table method, with 10 rats in each group. Except for the sham-operation group, the VaD model was prepared using a modified bilateral common carotid artery ligation method in all the groups. Xingnao Yisui Decoction high-, medium- and low-dosage groups were gavaged with 19.62, 9.81, 4.91 g/(kg·d) of Xingnao Yisui Decoction respectively, the donepezil group was gavaged with 0.5 mg/(kg·d) of donepezil solution, and the sham-operation group and the model group were given equal amount of saline gavage, 1 time/d for 4 weeks. Morris water maze experiment was used to observe the behavioral changes in each group, TUNEL staining was used to observe the apoptosis of neurons in CA1 area of hippocampus. Realtime PCR was used to detect the mRNA expression of NF-κB and MMP-9. ELISA was used to detect the changes of serum NF-κB, MMP-9, p53, Bcl-2 and Bax protein levels.Results:Compared with the model group, the escape latency of rats in the donepezil group and Xingnao Yisui Decoction high-, medium- and low-dosage groups was shortened ( P<0.05); the times of crossing the platform and the stay time in the target quadrant increased ( P<0.05); the number of apoptotic cells in hippocampal CA1 region decreased ( P<0.01); the number of apoptotic cells in hippocampal CA1 region decreased ( P<0.01); the mRNA expression of NF- κB and MMP-9 in hippocampal mRNA level decreased ( P<0.01); the content of NF-κB, MMP-9, p53 and Bax decreased ( P<0.01), while the content of Bcl-2 increased ( P<0.01). Conclusion:Xingnao Yisui Decoction can effectively mediate the NF-κB-MMP-9 pathway to improve the permeability of the blood-brain barrier and regulate p53-Bcl-2-Bax to reduce apoptosis of neurons in CA1 area of hippocampus, thus significantly improve the learning and memory ability of VaD rats.

Objective Performing physical tasks in the low-pressure environment of space poses a significant physiological challenge for astronauts.This study investigates the localized thermophysiological effects of typical physical tasks on different body segments and analyzes the mechanisms by which low-pressure environments influence human task performance.The findings aim to provide a theoretical basis for the thermal control design of spacesuits,focusing on both localized thermoregulation and overall task performance.Methods Two typical physical tasks—15 kg weighted walking and 25 kg load-carrying—were conducted in a simulated low-pressure composite environment chamber.The chamber was set to an altitude-equivalent pressure of 57 kPa(4500 m),with a temperature of 26℃and humidity of 40％.Six non-acclimatized adult male participants were recruited.After environmental stabilization,12-point skin temperatures were recorded throughout the tasks,and localized temperature data were statistically analyzed.Results Under low-pressure conditions,different body regions exhibited distinct thermal responses over time depending on the task type,while the same body region showed varied responses under different task conditions.During walking,temperatures in the primary active regions(thighs and calves)decreased,with most other body regions(except the pelvis and feet)gradually cooling as the task progressed.In contrast,during load-carrying,temperatures in the primary active regions(back and upper arm muscles)increased significantly.Conclusion Astronauts performing different tasks in low-pressure environments experience distinct localized thermophysiological effects.Therefore,spacesuit thermal control systems should not only account for task intensity and metabolic differences but also adapt localized heating/cooling based on task-specific thermal profiles.This approach enables targeted intelligent thermal regulation,enhancing operational support in specific mission scenarios.

Objective To investigate the relationships of CXC motif chemokine ligand 10(CXCL10)and CC motif chemokine ligand 11(CCL11)in the peripheral blood with type 2 diabetic osteoporosis(T2DOP),and to construct a predictive model.Methods A total of 260 patients with type 2 diabetes mellitus(T2DM)were prospectively selected as the T2DM group.They were divided into T2DOP group(n=82)and non-T2DOP group(n=178)according to the occurrence of T2DOP.Additionally,68 healthy volunteers with physical examinations in the same period were se-lected as control group.Enzyme-linked immunosorbent assay was used to detect the levels of CXCL10 and CCL11 in the peripheral blood as well as bone metabolism indicators[β-C-terminal te-lopeptide of type Ⅰ collagen(β-CTX),N-terminal propeptide of type Ⅰ procollagen(PⅠNP)].Pear-son correlation analysis was used to explore the correlation of CXCL10 and CCL11 in peripheral blood with bone metabolism indicator levels in patients with T2DM.Multifactor non-conditional Logistic regression analysis was used to explore the influencing factors of T2DOP and construct a pre-dictive model.The Hosmer-Lemeshow(H-L)test was used to assess the goodness of fit.The re-ceiver operating characteristic(ROC)curve analysis was used to evaluate the predictive value of each indicator and the predictive model for T2DOP,and decision curve analysis and Bootstrap resa-mpling were used for internal validation.Results Compared with the control group,the levels of CXCL10 and CCL11 in the peripheral blood as well as β-CTX in the T2DM group were significantly increased,while the level of P Ⅰ NP was significantly decreased(P＜0.05).Pearson correlation a-nalysis showed that CXCL10 and CCL11 in the peripheral blood in patients with T2DM were posi-tively correlated with β-CTX level(r=0.786,0.816,P＜0.001)and negatively correlated with P ⅠNP level(r=-0.675,-0.716,P＜0.001).Compared with the non-T2DOP group,the T2DOP group had significantly increased age and the ratio of diabetic nephropathy,prolonged dura-tion of diabetes,decreased body mass index(BMI)and P ⅠNP levels,and increased fasting blood glucose,glycated hemoglobin(HbA1c),β-CTX,CXCL10,and CCL11 levels(P＜0.05).Non-conditional Logistic regression analysis showed that advanced age,long duration of diabetes,high HbA1c,high CXCL10,and high CCL11 were independent risk factors for T2DOP(P＜0.05),while high BMI was an independent protective factor(P＜0.05).The ROC curve showed that the area under the curve(AUC)of the predictive model for predicting T2DOP was 0.919,which was significantly greater than the AUCs of 0.643,0.742,0.654,0.715,0.759 and 0.741 respectively for age,duration of diabetes,BMI,HbA1c,CXCL10 and CCL11 alone(Z=7.468,5.400,7.415,6.365,5.242,5.800,P＜0.001).After internal validation,the decision curve of the predictive model was higher than the two extreme curves.After 1,000 times of Bootstrap resampling internal validations,the concordance index of the predictive model was 0.919(95％CI,0.914 to 0.923).Conclusion Increased levels of CXCL10 and CCL11 in the peripheral blood are associat-ed with T2DOP,and the predictive model constructed based on these factors has a high predictive value for T2DOP.

Compared with acute pancreatitis caused by other factors， hyperlipidemic acute pancreatitis often has a higher rate of severe conditions， greater difficulties in predicting prognosis， and a more complex and unclear pathogenesis. At present， the pathogenesis of hyperlipidemic acute pancreatitis may be associated with the elevation of serum free fatty acids， but the lipid-lowering treatment regimens do not reduce the incidence rate of this disease. Recent studies have further confirmed that pancreatic duct hypertension is an important pathogenesis of acute pancreatitis. The latest research advances have shown that hyperlipidemia can lead to pancreatic duct obstruction by causing pancreatic duct hyperplasia， forming protein embolism at the biliary-pancreatic junction， and damaging the secretory function of the pancreatic duct， while pancreatic duct obstruction can in turn cause pancreatic duct obstruction. This article reviews the latest research advances in hyperlipidemia in causing pancreatic duct obstruction and emphasizes that pancreatic duct hypertension is one of the important pathogeneses of hyperlipidemic acute pancreatitis， which will provide new ideas for exploring the pathogenesis of hyperlipidemic acute pancreatitis.

Objective To investigate the role of homologous genes absent from the wings of drosophila melanogaster(Notch)signaling pathway in the imbalance of helper T cells 1(Th1)and helper T cells 2(Th2)and the intervention mechanism of Qizhi Zhoufei Granule in chronic obstructive pulmonary disease(COPD).Methods Ten of seventy Wistar rats were selected as the blank control group,and the other rats were established by cigarette smoking combined(CS)with tracheal infusion of lipopolysaccharide(LPS).The COPD model was established by randomly selecting 3 rats in the control group and the model group to verify the success of the model.At the end of modeling,gavage administration was performed.The rats in the model group were randomly divided into model control group,positive control group(67.5 μg·kg-1)and Qizhi Zhoufei Granule high,medium and low treatment group(3.24,1.62,0.81 g·kg-1).Each group was treated with normal saline,dexamethasone acetate suspension and Qizhi Zhoufei Granule suspension at high,medium and low doses.The rats in the blank control group were given the same volume of normal saline as the model control group.After modeling with 28 days and treatment with 28 days,peak inspiratory flow(PIF)and peak expiratory flow(PEF)were detected by the animal lung function test system.Rats were killed to extract lungs,spleen,serum and bronchoalveolar lavage fluid(BALF),hematoxylin-eosin(HE)staining was used to evaluate the pathological changes of lung tissues.The level of tumor necrosis factor-α(TNF-α)in serum and BALF was determined by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect Th1/Th2 cells in spleen.Immunohistochemistry(IHC)and western blot were used to detect Notch1,Hes1 and Hey1 protein levels in lung tissues.Real-time fluorescence quantitative polymerase chain reaction(Real-Time PCR)was used to detect Notch1,Hes1 and Hey1 gene expression levels in lung tissues.Result Compared with the blank control group,the lung function of the model control group was significantly decreased(P<0.05),inflammatory cell infiltration and bronchial structure destruction occurred in the lung tissue,TNF-α content in serum and BALF increased significantly(P<0.05),the percentage of spleen Th1 cells was significantly decreased(P<0.05),and the percentage of Th2 cells was significantly increased(P<0.05),the protein and mRNA expressions of Notch1,Hes1 and Hey1 in lung tissues were significantly increased(P<0.05),the differences were statistically significant;Compared with the model control group,the lung function of rats in each administration group was significantly increased(P<0.05),the pathological injury of lung tissue was alleviated,TNF-α content in serum and BALF decreased significantly(P<0.05),the percentage of spleen Th1 cells was significantly increased(P<0.05),the percentage of Th2 cells was significantly decreased(P<0.05),the lung tissue of Notch1,Hes1,Hey1 protein and mRNA expression were significantly decreased(P<0.05),the differences were statistically significant.Conclusion Qizhi Zhoufei Granule regulate Th1/Th2 balance by inhibiting Notch signaling pathway,thereby improving pulmonary function and pathological injury,and affecting immune function in COPD rats.

Objective:To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies(IIMs)patients receiving conventional treatment.Methods:Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were in-cluded.The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics,laboratory features,peripheral blood lymphocytes,immunological indicators,and therapeutic drugs.Results:Among the 635 patients included,518 patients finished the follow-up,with an average time of 36.8 months.The total complete clinical response rate of IIMs was 50.0％(259/518).The complete clinical response rate of dermatomyositis(DM),anti-synthetase syn-drome(ASS)and immune-mediated necrotizing myopathy(IMNM)were 53.5％,48.9％and 39.0％,respectively.Fever(P=0.002)and rapid progressive interstitial lung disease(RP-ILD)(P=0.014)were observed much more frequently in non-complete clinical response group than in complete clinical re-sponse group.The aspartate transaminase(AST),lactate dehydrogenase(LDH),D-dimer,erythrocyte sedimentation rate(ESR),C-reaction protein(CRP)and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group.As for the treat-ment,the percentage of glucocorticoid received and intravenous immunoglobin(IVIG)were significantly higher in non-complete clinical response group than in complete clinical response group.Risk factor analysis showed that IMNM subtype(P=0.007),interstitial lung disease(ILD)(P=0.001),eleva-ted AST(P=0.012),elevated serum ferritin(P=0.016)and decreased count of CD4+T cells in peripheral blood(P=0.004)might be the risk factors for IIMs non-complete clinical response.Conclu-sion:The total complete clinical response rate of IIMs is low,especially for IMNM subtype.More effec-tive intervention should be administered to patients with ILD,elevated AST,elevated serum ferritin or decreased count of CD4+T cells at disease onset.

Objective:To explore the effective indicators that can predict the poor prognosis of neonates with congenital heart disease after surgery.Methods:178 cases of neonatal congenital heart disease were retrospectively analyzed. According to the outcome, they were divided into normal prognosis group (132 cases) and poor prognosis group (46 cases).Results:15 (8.4%) patients died in hospital. There were statistical differences between the two groups in terms of whether PGE and vasoactive drugs were needed before surgery, preoperative respiratory support mode, blood lactate level from anesthesia induction to 24 h after surgery, VIS and VVR scores, whether delayed sternal closure or peritoneal dialysis were needed ( P<0.05). Logistic regression analysis showed that elevated lactate levels and VVR scores on 24 h after surgery were independent risk factors for death or other poor postoperative prognosis in neonates ( P<0.05). Conclusion:The levels of lactate and VVR scores in 24 h after operation are sensitive indicators for monitoring the severity of the condition, guiding treatment and judging prognosis of neonatal congenital heart disease surgery.

BACKGROUND:Osteoporosis is a disease in which bone density and structure are destroyed and fractures are caused by increased bone fragility,leading to high clinical disability and mortality rates. OBJECTIVE:To review the research progress in the role of bone immunity in physiological and pathological processes related to bone metabolism,providing ideas for the research and clinical application of bone immunity in bone diseases. METHODS:The first author searched PubMed and CNKI databases in November 2022 for relevant literature using the keywords of"osteoimmunology,immuno-skeletal interface,bone metabolism,skeletal metabolism,lymphocyte,immune factor"in English and Chinese,respectively.The time range of retrieval was mainly from January 2010 to November 2022,and a small number of classical long-term literatures were included.After reading the topic and abstract for preliminary screening and excluding repetitive studies,low-quality journals and unrelated literature,81 documents were finally included for review. RESULTS AND CONCLUSION:Osteoimmunology refers to that bone and immune cells share the same microenvironment and interact with each other to jointly perform the"bone immune system,"which includes all cells in the bone marrow.Immuno-skeletal interface has protective effects on bone under physiological conditions,but it may lead to bone destruction under pathological conditions.Osteoprotegerin is mainly derived from B cells and can inhibit osteoclast metabolism.However,when the body is in an inflammatory state,T cells and B cells work together to promote bone resorption.In addition,interleukin-1,interleukin-6 and tumor necrosis factor-α regulate the expression of receptor activator of nuclear factor-κB ligand in vivo and affect bone metabolism.In most clinical diseases(such as rheumatoid arthritis,estrogen deficiency,HIV infection,and hyperparathyroidism),the immuno-skeletal interface interacts with the bone immune system,resulting in the regulation of bone metabolism.In terms of clinical prospect,the interaction between bone immunity and bone metabolism should be studied in order to propose new strategies for therapeutic intervention to reduce the risk of fracture.

OBJECTIVE To evaluate the effects of ivabradine on vascular endothelial function in patients with coronary artery disease. METHODS PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang Data， VIP and CBM databases were retrieved to collect randomized controlled trials （RCTs） about ivabradine （intervention group） versus placebo or β-blocker （control group） from the inception to Mar. 20th 2023. The meta-analysis was performed by using RevMan 5.4 software after literature screening， data extraction and quality evaluation. RESULTS A total of 12 RCTs were included， involving 1 206 patients. The results of meta-analysis showed that the levels of flow-mediated dilation （FMD） [MD＝1.71， 95%CI （0.96， 2.46）， P＜0.000 01] and nitric oxide （NO） [MD＝5.80， 95%CI （5.02， 6.59）， P＜0.000 01] in the intervention group were significantly higher than control group， while endothelin-1（ET-1） level was significantly lower than control group [MD＝－7.45， 95%CI （－8.42， －6.47）， P＜0.000 01]. There was no statistical significance in nitroglycerin-mediated dilation （NMD） level between 2 groups [MD＝0.13， 95%CI（－0.74， 1.00）， P＝0.77]. Subgroup analyses based on the different medications and intervention time in the control group showed better improvement in FMD level of patients receiving ivabradine， compared with placebo （P＜0.05）； compared with placebo and β-blocker， the level of NO in patients receiving ivabradine was improved significantly （P＜0.05）， while ET-1 level was decreased significantly （P＜0.05）. Regardless of the duration of the intervention， the levels of FMD， NO， and ET-1 in the intervention group were significantly improved compared to the control group （P＜0.01）， while the difference in NMD was not statistically significant （P＞0.05）. CONCLUSIONS Ivabradine can improve vascular endothelial function in patients with coronary artery disease.