Based on the theory of "disease of both blood and water" in Essentials from the Golden Cabinet （《金匮要略》）， and in combination with the dynamic syndrome evolution of heart failure with preserved ejection fraction （HFpEF）， this paper systematically clarifies the pathomechanism of HFpEF， characterized by yang deficiency as the root， blood stasis as the pivotal factor and water retention as the manifestation. Accordingly， the therapeutic principles have been proposed， which are warming yang and banking up original qi to consolidate the root， activating blood and unblocking collaterals to smooth the mechanism， and promoting urination and regulating pivot to remove the branch. On this basis， a compound formula structure of "one monarch， one minister and one assistant" is established， forming an integrated intervention strategy that synergistically combines the three methods of warming yang， activating blood， and promoting urination through combined classical formulas. Zhenwu Decoction （真武汤）， which warms yang and dissolves rheum， is used to consolidate the root and directly target the source of yang deficiency， serving as the monarch； Guizhi Fuling Pills （桂枝茯苓丸）， which activates blood， promotes urination and unblocks the pivot， assists in interrupting the binding of blood stasis and water retention， serving as the minister； Tingli Dazao Xiefei Decoction （葶苈大枣泻肺汤）， which regulates qi， disperses retained fluids， and eliminates the manifestation， alleviates acute water-retention symptoms， serving as the assistant. This compound formula is warming without being drying， diuretic without being drastic， and dispels stasis without consuming blood， thereby achieving the therapeutic effects of warming yang， activating blood， and promoting urination.

The legal and regulatory system for the import of blood products in China has undergone a three-stage evolution of"safety first,demand-driven and standard upgrading",ultimately forming a dual control framework that centers on infectious disease prevention and control as well as quality approval.While the current policy effectively ensures biosafety,it also faces several deep-seated contradictions.These include the worsening imbalance between supply and demand,limited access to clinically needed blood products,and insufficient alignment with international standards.Moreover,strict regulation has also constrained technological innovation and market diversification.To address these challenges,it is suggested to establish a synergy mechanism that integrates a"clinical urgent need list,"hierarchical supervision,and mutual recognition of Good Manufacturing Practice(GMP).By implementing dynamic access,risk classification management,and international certification mutual recognition,it is possible to achieve compatible development between the safety baseline and medical accessibility.

Objective:To observe the effects of acupuncture on the motor function of Parkinson disease(PD)model mice and to investigate the neuroprotective effects of acupuncture on PD from the perspective of cellular senescence.Methods:C57BL/6J mice were randomly divided into a normal control(NC)group,a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)group,an acupuncture(ACU)group,and a rasagiline(RAS)group,with 6 mice in each group.Except for the mice in the NC group,all mice were injected intraperitoneally with MPTP[30 mg/(kg·bw)]to establish a PD mouse model.After the models were successfully established,mice in the ACU group received acupuncture at Baihui(GV20)and bilateral Yanglingquan(GB34)for 15 min,once a day for 14 consecutive days.Mice in the RAS group were treated with gavage of rasagiline mesylate[0.5 mg/(kg·bw)],once daily for 14 d.Mouse balance and motor functions were detected using the mouse fatigue rotating rod apparatus.Immunohistochemistry staining was used to detect the number of tyrosine hydroxylase(TH)-positive neurons and the protein expression levels of special AT-rich sequence-binding protein 1(SATB1),p21,and p53 in the substantia nigra(SN)region of the mouse brain in each group.The glutathione peroxidase(GSH-Px)activity of mouse brain SN tissue was detected by enzyme-linked immunosorbent assay.The protein expression levels of interleukin(IL)-6 and senescence-associated β-galactosidase(SA-β-gal)in the SN tissue of mice in each group were detected by Western blotting.The relative expression of SATB1,p21,and p53 mRNA in the SN of each group was detected by real-time quantitative polymerase chain reaction.Results:Compared to the NC group,the overall rod performance(ORP)score,the number of TH-positive neurons,and GSH-Px activity in the SN region were significantly lower in the mice in the MPTP group(P<0.01);compared to the MPTP group,the ORP score,the number of TH-positive neurons,and GSH-Px activity were significantly increased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly increased(P<0.01);compared to the MPTP group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly decreased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the relative expression of SATB1 protein and mRNA in the SN of mice in the MPTP group was significantly decreased(P<0.01);compared to mice in the MPTP group,mice in the ACU group and the RAS group showed significant increases in the relative expression of SATB1 protein and mRNA(P<0.01 or P<0.05).Conclusion:Acupuncture can improve motor function and increase the number of TH-positive neurons in the SN of PD model mice.Its neuroprotective effect may relate to the regulation of the SATB1/p21 signaling pathway and the inhibition of cellular senescence-related biomarker expression in the SN.

Luteolin is a natural flavonoid compound exists in various fruits and vegetables.Recent studies have indicated that luteolin has variety pharmacological effects,including a wide range of antidepressant properties.Here,we systematically review the preclinical studies and limited clinical evidence on the antidepressant and neuroprotective effects of luteolin to fully explore its antidepressant power.Network pharmacology and molecular docking analyses contribute to a better understanding of the preclinical models of depression and antidepressant properties of luteolin.Seventeen preclinical studies were included that combined network pharmacology and molecular docking analyses to clarify the antide-pressant mechanism of luteolin and its antidepressant targets.The antidepressant effects of luteolin may involve promoting intracellular noradrenaline(NE)uptake;inhibiting 5-hydroxytryptamine(5-HT)re-uptake;upregulating the expression of synaptophysin,postsynaptic density protein 95,brain-derived neurotrophic factor,B cell lymphoma protein-2,superoxide dismutase,and glutathione S-transferase;and decreasing the expression of malondialdehyde,caspase-3,and amyloid-beta peptides.The antide-pressant effects of luteolin are mediated by various mechanisms,including anti-oxidative stress,anti-apoptosis,anti-inflammation,anti-endoplasmic reticulum stress,dopamine transport,synaptic protec-tion,hypothalamic-pituitary-adrenal axis regulation,and 5-HT metabolism.Additionally,we identified insulin-like growth factor 1 receptor(IGF1R),AKT serine/threonine kinase 1(AKT1),prostaglandin-endoperoxide synthase 2(PTGS2),estrogen receptor alpha(ESR1),and epidermal growth factor recep-tor(EGFR)as potential targets,luteolin has an ideal affinity for these targets,suggesting that it may play a positive role in depression through multiple targets,mechanisms,and pathways.However,the clinical efficacy of luteolin and its potential direct targets must be confirmed in further multicenter clinical case-control and molecular targeting studies.

Objective:To observe the effects of acupuncture on the motor function of Parkinson disease(PD)model mice and to investigate the neuroprotective effects of acupuncture on PD from the perspective of cellular senescence.Methods:C57BL/6J mice were randomly divided into a normal control(NC)group,a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)group,an acupuncture(ACU)group,and a rasagiline(RAS)group,with 6 mice in each group.Except for the mice in the NC group,all mice were injected intraperitoneally with MPTP[30 mg/(kg·bw)]to establish a PD mouse model.After the models were successfully established,mice in the ACU group received acupuncture at Baihui(GV20)and bilateral Yanglingquan(GB34)for 15 min,once a day for 14 consecutive days.Mice in the RAS group were treated with gavage of rasagiline mesylate[0.5 mg/(kg·bw)],once daily for 14 d.Mouse balance and motor functions were detected using the mouse fatigue rotating rod apparatus.Immunohistochemistry staining was used to detect the number of tyrosine hydroxylase(TH)-positive neurons and the protein expression levels of special AT-rich sequence-binding protein 1(SATB1),p21,and p53 in the substantia nigra(SN)region of the mouse brain in each group.The glutathione peroxidase(GSH-Px)activity of mouse brain SN tissue was detected by enzyme-linked immunosorbent assay.The protein expression levels of interleukin(IL)-6 and senescence-associated β-galactosidase(SA-β-gal)in the SN tissue of mice in each group were detected by Western blotting.The relative expression of SATB1,p21,and p53 mRNA in the SN of each group was detected by real-time quantitative polymerase chain reaction.Results:Compared to the NC group,the overall rod performance(ORP)score,the number of TH-positive neurons,and GSH-Px activity in the SN region were significantly lower in the mice in the MPTP group(P<0.01);compared to the MPTP group,the ORP score,the number of TH-positive neurons,and GSH-Px activity were significantly increased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly increased(P<0.01);compared to the MPTP group,the protein levels of IL-6 and SA-β-gal in the SN tissue,the protein and mRNA expression levels of p21 and p53 were significantly decreased in the ACU group and the RAS group(P<0.01 or P<0.05).Compared to the NC group,the relative expression of SATB1 protein and mRNA in the SN of mice in the MPTP group was significantly decreased(P<0.01);compared to mice in the MPTP group,mice in the ACU group and the RAS group showed significant increases in the relative expression of SATB1 protein and mRNA(P<0.01 or P<0.05).Conclusion:Acupuncture can improve motor function and increase the number of TH-positive neurons in the SN of PD model mice.Its neuroprotective effect may relate to the regulation of the SATB1/p21 signaling pathway and the inhibition of cellular senescence-related biomarker expression in the SN.

Objective To observe the value of MRI radiomics combined with ResNet101 deep learning for differentiating lumbar spine brucella spondylitis(BS)and spinal metastases(SM).Methods Seventy-one cases of lumbar spine BS and the same amount of lumbar spine SM patients were retrospectively enrolled in training set,while 33 cases of lumbar spine BS and the same amount of lumbar spine SM patients were enrolled in test set.Clinical features were screened with univariate and multivariate logistic analysis,and a clinical model(Mclinic)was constructed.ROI of lesions were drawn on lumbar sagittal T 2WI,then radiomics features were extracted to construct a radiomics model(Mradiomics).ResNet101 deep learning was integrated with radiomics,then deep learning radiomics features were extracted to construct deep learning radiomics model(MDL+R).Finally a combined model(Mcombined)was constructed through combining clinical features and deep learning radiomics features.The efficacy of the above models for differentiating BS and SM were analyzed.Results Significant differences of patients' age and proportion of fever and accessory involvement were found between BS and SM patients in training and test sets(all P＜0.05),and univariate and multivariate logistic analysis showed the latter two were clinical features(both P＜0.001).The area under the curve(AUC)of Mclinic for differentiating lumbar spine BS and SM was 0.794 and 0.773 in training set and test set,of Mradiomics was 0.895 and 0.791,of MDL+R was 0.926 and 0.882,while of Mcombined was 0.967 and 0.906,respectively.AUC of Mcombined was the highest in training set(all P＜0.05),while in test set,AUC of Mcombined was significantly higher than that of Mclinic and Mradiomics(both P＜0.05).Conclusion MRI radiomics combined with ResNet101 deep learning was helpful for differentiating lumbar spine BS and SM.Combining with clinical data could improve its diagnostic efficacy.

The legal and regulatory system for the import of blood products in China has undergone a three-stage evolution of"safety first,demand-driven and standard upgrading",ultimately forming a dual control framework that centers on infectious disease prevention and control as well as quality approval.While the current policy effectively ensures biosafety,it also faces several deep-seated contradictions.These include the worsening imbalance between supply and demand,limited access to clinically needed blood products,and insufficient alignment with international standards.Moreover,strict regulation has also constrained technological innovation and market diversification.To address these challenges,it is suggested to establish a synergy mechanism that integrates a"clinical urgent need list,"hierarchical supervision,and mutual recognition of Good Manufacturing Practice(GMP).By implementing dynamic access,risk classification management,and international certification mutual recognition,it is possible to achieve compatible development between the safety baseline and medical accessibility.

Objective To investigate the critical role of macrophage M1 polarization in mediating the effect of periodontitis on the progression of chronic obstructive pulmonary disease(COPD).Methods Alveolar lavage fluid samples were collected from COPD patients with comorbid periodontitis,and gene expression analysis was performed to validate the changes in the expression of M1 polarization-related genes.A mouse model of COPD,with experimentally induced periodontitis,were established.Hematoxylin and eosin(HE)staining of pathological sections was performed to observe the effect of periodontitis on COPD progression.Flow cytometry,immunofluorescence staining,and reverse transcription quantitative polymerase chain reaction(RT-qPCR)were performed to analyze the effect of periodontitis on macrophage M1 polarization and the expression of relevant genes in the alveolar lavage fluid and lung tissues.Results In clinical samples of alveolar lavage fluid from COPD patients with periodontitis,the expression of macrophage M1 polarization-related genes,including CD86,inducible nitric oxide synthase(iNOS),interleukin(IL)-1β,tumor necrosis factor(TNF)-α,IL-23,and IL-6,was upregulated compared with that of COPD patients without periodontitis.Analysis of a mouse disease model revealed that periodontitis affected the growth of COPD mice,with the final body mass of mice in the periodontitis and COPD comorbid group([21.3±0.52]g,day 34)lower than that of the COPD group([23.93±0.45]g,day 34).Pathological sections of the lung tissue showed that periodontitis exacerbated COPD progression,with more pronounced alveolar expansion and alveolar wall destruction observed in the periodontitis and COPD comorbid group.Flow cytometry revealed a higher proportion of M1-polarized macrophages in alveolar lavage fluid from COPD and periodontitis comorbid mice([31.36±2.51]%)compared with the COPD mice([23.19±1.07]%).Immunofluorescence assays indicated that periodontitis also promoted macrophage M1 polarization in the lung tissue of COPD mice.Gene expression analysis demonstrated that M1 polarization-related gene expression was significantly upregulated in both the alveolar lavage fluid and lung tissue of mice in the COPD and periodontitis co-morbid group compared to the COPD group.Conclusion Periodontitis exacerbates COPD progression by promoting macrophage M1 polarization in the lungs.Enhancing oral hygiene management and targeting the inhibition of macrophage M1 polarization may represent new therapeutic strategies for the clinical prevention and control of COPD.

Objective To compare the analgesic effects and adverse reactions between intercostal nerve block (ICNB) and patient controlled intravenous analgesia (PCIA). Methods From August 2022 to January 2023, 180 patients with lung cancer who underwent thoracoscopic surgery were randomly divided into two groups: ICNB group (n=90) and PCIA group (n=90). The postoperative pain degree (VAS), location, nature; adverse events, such as nausea, vomiting, and dizziness; and other clinical symptoms were analyzed. Results The most common site of postoperative pain in both groups was surgical incision, and the nature of pain was distending pain. At 12 and 24 h after the operation, the pain degree in the ICNB group (1.10±0.91, 3.12±1.29) was markedly lower than that in PCIA group (1.44±0.86, 4.32±1.30, P=0.010, P<0.001). The incidence of nausea, vomiting, and dizziness in the ICNB group (5.56%, 23.33%) was noticeably lower than that in the PCIA group (35.56%, 51.11%, P<0.001, P<0.001). Total hospitalization expense in the ICNB group (41 043.16±10 885.63 yuan) was significantly lower than that in PCIA group (45 283.99±11 036.36 yuan, P=0.010). Conclusion The analgesic effect of intercostal nerve block is better than that of patient-controlled intravenous analgesia pump in patients with lung cancer after minimally invasive surgery, and the incidence of adverse reactions is low.

Objective:To dynamically assess liver fibrosis using magnetic resonance elastography (MRE) and explore factors associated with fibrosis reversal in patients with metabolic dysfunction-associated steatohepatitis (MASH).Methods:This study included data from patients diagnosed with MASH by liver biopsy who underwent at least two MRE examinations. Patients were divided into a fibrosis reversal group and a non-reversal group according to whether MRE values decreased by 20% during follow-up. Differences in clinical data between the groups were compared using analysis of variance, the Kruskal-Wallis test, and the chi-square test. Univariate and multivariate logistic regression analyses were used to explore independent risk factors for fibrosis reversal in MASH.Results:A total of 46 cases were included in this study (mean age 50.1±12.3 years, BMI 26.1±3.1 kg/m2). Among them, the reversal group accounted for 26.1%. The rate of decrease in MRI proton density fat fraction (PDFF) was significantly higher in the reversal group (-50.0% vs. -8.1%, P=0.001) than in the non-reversal group between the two MRE examinations. The reversal group showed a more significant change rate of decreases in fasting insulin (-37.3% vs. -3.6%, P=0.011), insulin resistance index (-38.6% vs. -6.5%, P=0.044), and ALP (-24.9% vs. 0, P=0.004). Multivariate logistic regression analysis indicated that the rate of change in MRI PDFF was an independent predictor of fibrosis reversal ( OR=0.96, 95% CI: 0.92-1.00, P=0.046). Conclusion:A decrease in MRI proton density fat fraction levels is independently associated with liver fibrosis reversal in MASH, suggesting that intervention targeting liver fat content may be an effective treatment strategy.