Chronic heart failure （CHF） is a group of complex clinical syndromes caused by abnormal changes in the structure and/or function of the heart due to various reasons， resulting in disorders of ventricular contraction and/or diastole. CHF is a condition where primary diseases such as coronary heart disease， hypertension and pulmonary heart disease recur frequently and persist for a long time， presenting blood stasis in meridians and collaterals， stagnation of water and dampness， and accumulation of Qi in collaterals. Its pathogenesis is complex and may involve myocardial energy metabolism disorders， oxidative stress responses， myocardial cell apoptosis， autophagy， inflammatory responses， etc. According to the theory of restraining hyperactivity to acquire harmony， we believe that under normal circumstances， the adenosine monophosphate-activated protein kinase （AMPK） signaling pathway functions normally， maintaining human physiological activities and energy metabolism. Under pathological conditions， the AMPK signaling pathway is abnormal， causing energy metabolism disorders， inflammatory responses， and myocardial fibrosis. Traditional Chinese medicine （TCM） can regulate the AMPK signaling pathway through multiple mechanisms， targets， and effects， effectively curbing the occurrence and development of CHF. It has gradually become a research hotspot in the prevention and treatment of this disease. Guided by the theory of TCM， our research group， through literature review， summarized the relationship between the AMPK pathway and CHF and reviewed the research progress in the prevention and control of CHF with TCM active ingredients， TCM compound prescriptions， and Chinese patent medicines via regulating the AMPK pathway. The review aims to clarify the mechanism and targets of TCM in the treatment of CHF by regulating the AMPK pathway and guide the clinical treatment and drug development for CHF.

ObjectiveTo investigate the immunological characteristics of the patients with aplastic anemia （AA） and elevated hemogram parameters treated with Yiqi Yangxue prescription combined with Western medicine and the predictive effects of immunological indexes on elevated hemogram parameters， thus providing a reference for the prediction of the treatment efficacy and the adjustment of the treatment regimen. MethodA retrospective study was conducted， involving 77 AA patients treated with Yiqi Yangxue prescription combined with Western medicine for 6 months in 19 medical institutions including Xiyuan Hospital， China Academy of Chinese Medical Sciences from September 2018 to March 2021. The patients were assigned into two groups according to the elevations in hemogram parameters ［including hemoglobin （HGB）， white blood cell count （WBC）， platelet （PLT）， and absolute neutrophil count （ANC）］ after 6 months of treatment. One group had the elevation <50%， and the other group had the elevation ≥50% compared with the baseline. The clinical and immunological characteristics were compared between the two groups. Result① Compared with the group with HGB elevation<50%， the group with HGB elevation≥50% showed elevated level of CD3⁺ human leukocyte antigen-DR （HLA-DR）⁺ and increased proportion of patients with T-helper cell type 2 （Th2）<5%， CD8⁺≥50%， and CD3⁺HLA-DR⁺≥9% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD8⁺≥50% before treatment was the independent influencing factor for HGB elevation ≥50% ［odds ratio （OR）=12.000， 95% confidence interval （CI） 2.218， 64.928， P<0.01］. ② Compared with the group with WBC elevation<50%， the group with WBC elevation≥50% showed increased proportion of patients with CD3⁺HLA-DR⁺<6% and T-box transcription factor （T-bet）≥200% before treatment （P<0.05）. The multivariate Logistic regression analysis showed that CD3⁺HLA-DR⁺<6% （OR=2.998， 95%CI 1.036， 8.680， P<0.05） and T-bet≥200% （OR=3.634， 95%CI 1.076， 12.273， P<0.05） before treatment were independent influencing factors for WBC elevation≥50%. ③ Compared with the group with PLT elevation<50%， the group with PLT elevation≥50% presented lowered Th1 and CD3⁺HLA-DR⁺ levels and increased proportion of patients with Th1<12%， CD4⁺≥6%， and CD3⁺HLA-DR⁺<5% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD3⁺HLA-DR⁺<5% before treatment was the independent influencing factor for PLT elevation≥50% （OR=16.190， 95%CI of 3.430 to 76.434， P<0.01）. ④ Compared with the group with ANC elevation<50%， the group with ANC elevation≥50% showed no significant changes in the hemogram parameters before treatment. ConclusionAs for the AA patients with rapid elevation in HGB， Yiqi Yangxue prescription combined with Western medicine demonstrate significant effects in the patients with Th2<5% and CD3⁺HLA-DR⁺≥9%， especially those with CD8⁺≥50%. As for the AA patients with rapid elevation in WBC， the therapy was particularly effective in the patients with CD3⁺HLA-DR⁺<6% and T-bet≥200%. As for the AA patients with rapid growth in PLT， the therapy was particularly effective in the patients with Th1<12% and CD4⁺≥6%， especially those with CD3⁺HLA-DR⁺<5%.

BACKGROUND:Sepsis-induced systemic inflammation leads to rapid bone mass loss;however,there is a lack of effective treatments.Ulinastatin is an anti-inflammatory drug,but its protective effect and mechanism on bone under sepsis-induced systemic inflammation are still unclear. OBJECTIVE:To explore whether ulinastatin can relieve acute bone loss caused by lipopolysaccharide. METHODS:(1)Animal experiment.Thirty male C57BL/6 mice were randomly divided into three groups(n=10 per group):control group,model group and experimental group.The control group was injected intraperitoneally with normal saline,the model group was injected intraperitoneally with lipopolysaccharide,and the experimental group was injected intraperitoneally with lipopolysaccharide and ulinastatin.In the experimental group,ulinastatin was injected continuously for 3 days.After intraperitoneal injection of ulinastatin for 14 days,femoral tissues were taken for CT scanning and pathological observation.(2)Cell experiment.C57BL/6 mouse primary osteoblasts were isolated and divided into three groups:the control group was routinely cultured,lipopolysaccharide was added to the model group,and lipopolysaccharide with ulinastatin was added to the experimental group.Cell proliferation and osteogenic differentiation were detected.C57BL/6 mouse bone marrow mononuclear cells were isolated and divided into three groups:the control group was routinely cultured,lipopolysaccharide was added to the model group,and lipopolysaccharide and ulinastatin were added to the experimental group.Osteoclast differentiation was detected. RESULTS AND CONCLUSION:(1)Animal experiment.CT scanning and hematoxylin-eosin staining showed that bone mass in lipopolysaccharide-treated mice was reduced but increased after treatment with ulinastatin.Tartrate resistant acid phosphatase staining showed that the number of osteoclasts in bone tissue increased in the model group,but significantly decreased in the experimental group compared with the model group.(2)Cell experiment.Cell counting kit-8 assay showed that lipopolysaccharide treatment inhibited the proliferation of osteoblasts,and ulinastatin elevated the proliferation of osteoblasts after lipopolysaccharide treatment.Alkaline phosphatase staining,alizarin red staining and osteogenesis-related gene(alkaline phosphatase,Runx2,osteocalcin,osteoblastin,nuclear factor κB receptor-activating factor ligand,osteoprotegerin)detection showed that lipopolysaccharide treatment inhibited osteogenic differentiation of osteoblasts and elevated the nuclear factor κB receptor-activating factor ligand/osteoprotegerin ratio;ulinastatin did not have any significant effect on the reduction of osteoblast function induced by lipopolysaccharide but decreased the nuclear factor κB receptor-activating factor ligand/osteoprotegerin ratio.Tartrate resistant acid phosphatase staining and osteoclast-related gene(tartrate resistant acid phosphatase and matrix metalloproteinase 9)detection showed that lipopolysaccharide treatment could promote osteoclast differentiation of bone marrow monocytes,while ulinastatin could inhibit lipopolysaccharide-induced osteoclast differentiation of bone marrow monocytes.(3)Overall,ulinastatin can significantly inhibit lipopolysaccharide-induced bone loss,mainly through promoting osteoblast proliferation and directly or indirectly inhibiting osteoclast differentiation to alleviate bone loss and achieve osteoprotective effects.

Objective: To explore the impact of smart physical education assignment on physical health of male university students, so as to provide theoretical support and practical references for physical health improvement of male university students and implementing smart sports assignments. Methods: From September 2023 to January 2024, 317 sophomore male students from six Taekwondo elective classes at Hunan Institute of Engineering were selected and were randomly divided into an intervention group (n=157) and a control group (n=160). The intervention group was given sports assignments twice a week through smart means with an intervention duration of 15 weeks, each time for 25-35 minutes, in addition to the teaching according to the public course syllabus, while the control group was taught according to the public course syllabus. The physical and health indicators of both groups were tested before and after intervention,then the differences in various physical health indicators between two groups of students before and after intervention were compared through ttest and Mann-Whitney U test. Results: After the intervention, the vital capacity, 50 m run, sitandreach, 1 000 m run, and pullup scores of the intervention group significantly improved compared to those before intervention. The scores improved from (3 918.27±737.34)mL, 7.88(7.53,8.45)s, 9.80(2.70,15.75) cm, 4.30(4.12,4.50) min and 3.00(0.00,7.50) times to (4 574.19±800.61) mL, 7.65(7.37,8.12)s, 17.20(11.80,21.55)cm, 4.13(3.58,4.31)min and 5.00(1.00,10.00) times,respectively (t/Z=-7.60, 2.61, -8.39, 5.62, -2.72, P<0.05). Before intervention, there was no statistically significant difference in physical health indicators between the intervention group and the control group (P>0.05).After intervention,the scores of the intervention group on the vital capacity,50 m run,sitandreach,1 000 m run and pullup, were significantly higher than those of the control group [(4 310.97±808.90)mL, 7.75(7.40,8.30)s, 14.10(8.42,17.87)cm, 4.29(4.08,4.45)min and 4.00(1.00,7.00) times] (t/Z=2.91, -4.55, -4.75, -4.15, 2.58, P<0.05). Conclusions Having 25-35 min smart physical education assignment twice a week can effectively improve physical health level of male college students. It is recommended to assign appropriate amount of smart sports homework to improve physical health level of college students, while ensuring the amount and intensity of physical activity in public physical education courses.

Sepsis is one of the leading causes of death in intensive care unit(ICU)patients,typically resulting from excessive inflammation induced by infection,leading to multiple organ dysfunction syndrome and life-threatening complications.Exosomes are a type of extracellular vesicle that are lipid bilayered nanoparticles secreted by cells.In recent years,numerous studies have demonstrated their involvement in the occurrence and development of sepsis.The various molecular substances carried by exosomes have been shown to regulate sepsis-related inflammation and organ damage.In particular,different types of exosomes hold promise as diagnostic biomarkers for sepsis patients,and also provide new therapeutic targets for improving patient outcomes.This review was conducted on the research progress concerning the relationship between exosomes and sepsis,sepsis associated-acute lung injury(SA-ALI),sepsis associated encephalopathy(SAE),sepsis associated-acute kidney injury(SA-AKI),sepsis associated cardiomyopathy(SIC),and other organ injuries related to sepsis.This study aims to assist in guiding clinical diagnosis and treatment.

Nonalcoholic fatty liver disease(NAFLD)has developed into the most common chronic liver disease and can lead to liver cancer.Our laboratory previously developed a novel prescription for NAFLD,"Eight Zhes Decoction"(EZD),which has shown good curative effects in clinical practice.However,the pharmaco-dynamic material basis and mechanism have not yet been revealed.A strategy integrating lipidomics,network pharmacology and pharmacokinetics was used to reveal the active components and mecha-nisms of EZD against NAFLD.The histopathological results showed that EZD attenuated the degrees of collagen deposition and steatosis in the livers of nonalcoholic steatofibrosis model mice.Furthermore,glycerophospholipid metabolism,arachidonic acid metabolism,glycerolipid metabolism and linoleic acid metabolism with phospholipase A2 group IVA(PLA2G4A)and cytochrome P450 as the core targets and 12,13-cis-epoxyoctadecenoic acid,12(S)-hydroxyeicosatetraenoic acid,leukotriene B4,prostaglandin E2,phosphatidylcholines(PCs)and triacylglycerols(TGs)as the main lipids were found to be involved in the treatment of NAFLD by EZD.Importantly,naringenin,artemetin,canadine,and bicuculline were iden-tified as the active ingredients of EZD against NAFLD;in particular,naringenin reduces PC consumption by inhibiting the expression of PLA2G4A and thus promotes sufficient synthesis of very-low-density lipoprotein to transport excess TGs in the liver.This research provides valuable data and theoretical support for the application of EZD against NAFLD.

ObjectiveTo explore the predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating aplastic anemia （AA） in non-elderly adults， so as to provide a reference for predicting the prognosis of this therapy. MethodA retrospective study was conducted with the clinical data of non-elderly adult AA patients who visited 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 and were treated with Yiqi Yangxue Prescription combined with western medicine. According to the efficacy evaluation results at the 6^th month of treatment， the patients were assigned into effective and ineffective groups. The two groups were compared in terms of the gender， age， disease classification ［non-severe aplastic anemia （NSAA）/severe aplastic anemia （SAA）］， course of disease， family history， complications， history of drug allergy， baseline blood routine examination ［hemoglobin （HGB）， white blood cell （WBC）， neutrophil （ANC）， platelet （PLT）， and reticulocyte （Ret）］， T lymphocyte subsets， degree of proliferation of nucleated cells in bone marrow， and expression of T-bet and GATA-3. ResultA total of 101 non-elderly adult AA patients were enrolled in this study， including 81 in the effective group and 20 in the ineffective group. The effective group had a higher proportion of the patients without a history of drug allergy than the ineffective group （P<0.05）. The body height， body weight， gender， age， disease classification， course of disease， family history， and complications showed no significant differences between two groups. The effective group had higher levels of ANC and PLT before treatment （P<0.05） and higher proportion of patients with ANC≥1.6×10⁹/L and PLT≥25×10⁹/L （P<0.05， P<0.01） than the ineffective group. The baseline levels of WBC， HGB， and Ret showed no significant statistical differences between two groups. The levels of CD3⁺HLA-DR⁺T cells in the effective group before treatment was higher than that in the ineffective group （P<0.05）. The levels of CD3⁺CD19^-T cells， CD4⁺T cells， CD8⁺T cells， Th1 cells， Th2 cells， and CD3⁺CD25⁺T cells showed no significant statistical differences between two groups before treatment. The proportion of patients with active bone marrow nucleated cells proliferation in the effective group before treatment were significantly higher than that in the ineffective group, while the proportion of patients with reduced or extremely reduced proliferation were significantly lower than that in the ineffective group （P<0.05）. The expression levels of T-bet and GATA-3 genes had no significant differences between two groups before treatment. The multivariate binary logistic regression analysis showed that the ANC level before treatment and history of drug allergy were independent influencing factors for efficacy （P<0.05， P<0.01）， while other indicators were not influencing factors for efficacy. The receiver operating characteristic （ROC） curve was applied to analyze the predictive value of the ANC level before treatment in the treatment of AA in non-elderly adults with Yiqi Yangxue prescription combined with western medicine. The area under the curve was 0.679 （P<0.05）， with the critical value of 1.595×10⁹/L， the sensitivity of 0.42， and the specificity of 0.95. ConclusionThe history of drug allergy， pre-treatment ANC， PLT， CD3⁺HLA-DR⁺ T cell levels， and proliferation of nucleated cells in bone marrow before treatment are predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating AA in non-elderly adults. This therapy tends to be more effective for the patients with no history of drug allergy， higher ANC and PLT levels before treatment， especially those with ANC≥1.6×10⁹/L， PLT≥25×10⁹/L， and higher CD3⁺ HLA-DR⁺T cell levels and the more active proliferation of nucleated cells in bone marrow before treatment.

Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy, resulting in abnormal sensation in lower lip. It is generally believed that spontaneous sensory recovery in this nerve injury is difficult. However, during our follow-up, patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery. In this study, a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery. A mental nerve transection model of Thy1-YFP mice and tissue clearing technique were used to explore possible mechanisms in this process. Gene silencing and overexpression experiments were then conducted to detect the changes in cell morphology and molecular markers. In our follow-up, 75% of patients with unilateral inferior alveolar nerve neurectomy had complete sensory recovery of the lower lip 12 months postoperatively. Patients with younger age, malignant tumors, and preservation of ipsilateral buccal and lingual nerves had a shorter recovery time. The buccal nerve collateral sprouting compensation was observed in the lower lip tissue of Thy1-YFP mice. ApoD was demonstrated to be involved in axon growth and peripheral nerve sensory recovery in the animal model. TGF-β inhibited the expression of STAT3 and the transcription of ApoD in Schwann cells through Zfp423. Overall, after sacrificing the inferior alveolar nerve, the collateral compensation of the ipsilateral buccal nerve could innervate the sensation. And this process was regulated by TGF-β-Zfp423-ApoD pathway.
Mice ; Animals ; Lip/innervation* ; Prospective Studies ; Mandibular Nerve/pathology* ; Sensation/physiology* ; Trigeminal Nerve Injuries/pathology*

Pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine (GEM) with the molecular-targeted drug erlotinib (Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuli-responsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment via simultaneous delivery of small interference RNA (siRNA) for synergistic pancreatic cancer treatment. This "all-in-one" delivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhibitory effects on the proliferation and migration of tumor cells in vitro. Excitingly, the systemic injection of such a biomimetic drug co-delivery system not only resulted in superior inhibitory effects against orthotopic pancreatic tumor and patient-derived tumor (PDX), but also greatly extended the survival rate of tumor-bearing mice. Our findings provide a promising therapeutic strategy against pancreatic cancer through the enhanced synergistic effect of target therapy, chemotherapy and anti-fibrotic therapy, which represents an appealing way for pancreatic cancer treatment.