Objective To establish a stable and reliable sepsis model of rat after liver transplantation (LT) for clinical translational research and analyze its characteristics. Methods The "two-sleeve method" was used to establish the in situ LT model of SD rats, and the sepsis model was constructed through cecal ligation and puncture (CLP) at 3 d after the operation. SD rats were randomly divided into 3 groups: sham operation group (Sham group), LT group, and LT + CLP group, with 6 rats in each group. The changes in body weight, rectal temperature and survival rate were compared, and the sepsis score was used for evaluation. The levels of blood biochemical indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (Urea), creatinine (Cr), creatine kinase (CK), lactate dehydrogenase (LDH)] and inflammatory factors [interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α] in each group were detected, and the pathological changes and cell apoptosis in different organs were observed. Results Compared with the Sham group, the body weight of the LT group and LT + CLP group decreased (all P<0.05). The rectal temperature of the LT + CLP group showed a continuous downward trend after the operation, the sepsis score increased sharply after the operation, and the survival rate dropped to 16.7%, and the differences between the Sham group, LT group and LT + CLP group were statistically significant (all P<0.05). The levels of ALT, AST, Urea, Cr, CK, LDH, and serum IL-1β, IL-6, IL-10 and TNF-α in the LT + CLP group were higher than those in the Sham group and LT group rats within 72 hours after the operation(all P<0.05). The pathological examination of the LT + CLP group showed severe tissue structure destruction, necrosis and infiltration of inflammatory cells in multiple organs, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining showed an increased level of cell apoptosis in multiple organs. Conclusions Using liver transplantation combined with CLP, a stable animal model of liver transplantation infection is successfully established, which exhibits a high mortality rate, significant multi-organ damage and intense inflammatory response, providing an ideal animal model for transplantation infection research.

Chronic heart failure （CHF） is an end-stage cardiac syndrome driven by multiple factors. Its pathological process involves interactions of multiple pathways such as energy metabolism dysfunction， neuroendocrine dysregulation， and myocardial fibrosis. Although current clinical medicine can alleviate symptoms through single-target approaches， significant limitations in reversing cardiac remodeling and disease progression remain. Puerarin， a major bioactive isoflavone constituent derived from Pueraria lobata， exhibits multidimensional pharmacological effects， such as vasodilatory effects， regulation of neuroendocrine balance， enhancement of metabolic homeostasis， and suppression of myocardial apoptosis. This review systematically integrated puerarin's multi-target regulatory network， elucidating its mechanisms such as improving energy metabolism by AMP-activated protein kinase/mechanistic target of rapamycin （AMPK/mTOR） pathway， inhibiting fibrosis mediated by transforming growth factor-β （TGF-β）/Smad signals， and attenuating oxidative-inflammatory cascades by regulating nuclear factor erythroid 2 （E₂）-related factor 2/nuclear transcription factor-κB（Nrf2/NF-κB） axis. Clinical research data was used to validate its efficacy in improving the left ventricular ejection function and reducing the therapeutic potential of cardiovascular events' risks. The study proposed that puerarin's "systemic regulation" characteristic breaks through the limitations of traditional single-target drugs and prospected its clinical translation pathway based on metabolomics and nano-delivery technology， offering an integrative perspective from molecular mechanisms to precise therapy for the research on modernization of traditional Chinese medicine.

Chronic heart failure （CHF） is an end-stage cardiac syndrome driven by multiple factors. Its pathological process involves interactions of multiple pathways such as energy metabolism dysfunction， neuroendocrine dysregulation， and myocardial fibrosis. Although current clinical medicine can alleviate symptoms through single-target approaches， significant limitations in reversing cardiac remodeling and disease progression remain. Puerarin， a major bioactive isoflavone constituent derived from Pueraria lobata， exhibits multidimensional pharmacological effects， such as vasodilatory effects， regulation of neuroendocrine balance， enhancement of metabolic homeostasis， and suppression of myocardial apoptosis. This review systematically integrated puerarin's multi-target regulatory network， elucidating its mechanisms such as improving energy metabolism by AMP-activated protein kinase/mechanistic target of rapamycin （AMPK/mTOR） pathway， inhibiting fibrosis mediated by transforming growth factor-β （TGF-β）/Smad signals， and attenuating oxidative-inflammatory cascades by regulating nuclear factor erythroid 2 （E₂）-related factor 2/nuclear transcription factor-κB（Nrf2/NF-κB） axis. Clinical research data was used to validate its efficacy in improving the left ventricular ejection function and reducing the therapeutic potential of cardiovascular events' risks. The study proposed that puerarin's "systemic regulation" characteristic breaks through the limitations of traditional single-target drugs and prospected its clinical translation pathway based on metabolomics and nano-delivery technology， offering an integrative perspective from molecular mechanisms to precise therapy for the research on modernization of traditional Chinese medicine.

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Diabetes is a very complex endocrine disease whose common feature is the increase in blood glucose concentration. Persistent hyperglycemia can lead to blindness, kidney and heart disease, neurodegeneration, and many other serious complications that have a significant impact on human health and quality of life. The number of people with diabetes is increasing yearly. The global diabetes prevalence in 20-79 year olds in 2021 was estimated to be 10.5% (536.6 million), and it will rise to 12.2% (783.2 million) in 2045. The main modes of intervention for diabetes include medication, dietary management, and exercise conditioning. Medication is the mainstay of treatment. Marketed diabetes drugs such as metformin and insulin, as well as GLP-1 receptor agonists, are effective in controlling blood sugar levels to some extent, but the preventive and therapeutic effects are still unsatisfactory. Peptide drugs have many advantages such as low toxicity, high target specificity, and good biocompatibility, which opens up new avenues for the treatment of diabetes and other diseases. Currently, insulin and its analogs are by far the main life-saving drugs in clinical diabetes treatment, enabling effective control of blood glucose levels, but the risk of hypoglycemia is relatively high and treatment is limited by the route of delivery. New and oral anti-diabetic drugs have always been a market demand and research hotspot. Inhibitor cystine knot (ICK) peptides are a class of multifunctional cyclic peptides. In structure, they contain three conserved disulfide bonds (C3-C20, C7-C22, and C15-C32) form a compact “knot” structure, which can resist degradation of digestive protease. Recent studies have shown that ICK peptides derived from legume, such as PA1b, Aglycin, Vglycin, Iglycin, Dglycin, and aM₁, exhibit excellent regulatory activities on glucose and lipid metabolism at the cellular and animal levels. Mechanistically, ICK peptides promote glucose utilization by muscle and liver through activation of IR/AKT signaling pathway, which also improves insulin resistance. They can repair the damaged pancrease through activation of PI3K/AKT/Erk signaling pathway, thus lowering blood glucose. The biostability and hypoglycemic efficacy of the ICK peptides meet the requirements for commercialization of oral drugs, and in theory, they can be developed into natural oral anti-diabetes peptide drugs. In this review, the structural properties, activity and mechanism of ICK pattern peptides in regulating glucose and lipid metabolism were summaried, which provided a reference for the development of new oral peptides for diabetes.

BACKGROUND:Deep muscle stimulation has the effects of releasing muscle adhesion,relieving muscle spasm,improving and restoring muscle compliance and elasticity.Electromyographic biofeedback therapy can promote nerve recovery and improve lower limb motor function and gait. OBJECTIVE:To observe the effect of the effect of deep muscle stimulation combined with electromyographic biofeedback therapy on the spasm of the triceps surae and gait changes after stroke by using a digital muscle detector and three-dimensional gait analysis system. METHODS:A total of 72 patients who met the inclusion criteria were selected from the Rehabilitation Department of the First Affiliated Hospital of Guangdong Pharmaceutical University from October 2020 to October 2023.And they were enrolled and randomly divided into two groups(n=36 per group):a control group and a combined group.The control group received routine rehabilitation therapies,electromyographic biofeedback and pseudo deep muscle stimulation,while the combined group received true deep muscle stimulation treatment on the basis of the control group,five times per week,for 4 consecutive weeks.The oscillation frequency and dynamic stiffness of the affected gastrocnemius muscle,active range of motion of the ankle dorsiflexion muscle,electromyographic signal of the tibialis anterior muscle,Fugl-Meyer assessment of the lower limbs,and three-dimensional gait analysis parameters were statistically analyzed before and after treatment in two groups. RESULTS AND CONCLUSION:After treatment,oscillation frequency and dynamic stiffness values of the inner and outer sides of the affected gastrocnemius muscle in both groups of patients were significantly reduced compared with before treatment(P<0.05),and the combined group showed a more significant decrease compared with the control group(P<0.05).The active range of motion of the ankle dorsiflexion muscle,electromyographic signal of the tibialis anterior muscle,and Fugl-Meyer scores after treatment were significantly increased or improved compared with before treatment(P<0.05),while the combined group showed a more significant increase or improvement compared with the control group(P<0.05).In terms of gait parameters,the walking speed,frequency,and stride in both groups of patients were significantly increased compared with before treatment(P<0.05),while the combined group showed a more significant increase compared with the control group(P<0.05).The percentage time of support phase on the healthy side was shortened compared with before treatment(P<0.05),while the combined group showed a more significant decrease compared with the control group(P<0.05).In addition,there was no significant difference between the two groups except for the percentage of healthy side support(P>0.05).To conclude,the combination of deep muscle stimulation and electromyographic biofeedback can effectively alleviate triceps spasm in the short term after stroke,improve ankle dorsiflexion function,enhance lower limb motor function,and improve gait.The treatment effect is significant and worthy of clinical promotion and application.

Objective:To investigate relationship between expression of ADGRG5 and clinical prognosis and immune response in pancreatic adenocarcinoma(PAAD).Methods:ADGRG5 expression in PAAD and normal tissues were compared by Wilcoxon rank sum test.Diagnostic value of ADGRG5 was evaluated by ROC curve in PAAD.Kaplan-Meier method and Cox regres-sion analysis were used to evaluate prognostic factors.Gene set enrichment analysis(GSEA)and immune infiltration analysis were applied to annotate biological function of ADGRG5.Results:ADGRG5 expression in PAAD was significantly higher than normal tissue(P=2.8e-32).ADGRG5 had significant diagnostic and prognostic ability for PAAD(AUC=0.866).High ADGRG5 expression predicted a good progress free interval(PFI)(P=0.01),and expression of ADGRG5 was independently associated with PFI(HR:0.656,95%CI:0.433～0.972,P=0.035).ADGRG5 expression was related to regulation of immunomodulatory pathway and function of some types of immune infiltrating cells.Conclusion:Increased ADGRG5 may be a potential biomarker for PAAD diagnosis and prognosis,which affects prognosis of PAAD patients and significantly correlated with immune infiltration.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin,liquiritin apioside,verbascoside,narirutin,isoacteoside,apigetrin,hesperidin,isoliquiritin,ononin,liquiritigenin,glycyrrhizic acid,isoliquiritigenin,honokiol,obovatol,pogostone and magnolol in Jiawei Huoxiang Zhengqi Soft Capsules.METHODS The analysis was performed on a 40 ℃ thermostatic ZORBAX Eclipse Plus C18 column(2.1 mm×100 mm,1.8 μm),with the mobile phase comprising of 0.1％formic acid-acetonitrile flowing at 0.4 mL/min in a gradient elution manner,and electron spray ionization source was adopted in positive and negative ion scanning with multiple reaction monitoring mode.RESULTS Sixteen constituents showed good linear relationships within their own ranges(r＞0.990 0),whose average recoveries were 83.74％-105.12％with the RSDs of 1.10％-4.8％.CONCLUSION This accurate,sensitive,stable and reproducible method can provide a reference for the overall quality control of Jiawei Huoxiang Zhengqi Soft Capsules.

microRNA(miRNA),as a short non-coding RNA molecule,regulates bone-immune signal and stress response through transcription,translation as well as the combination of shear process,exerting the effect of promoting angiogenesis and repairing damage bone;type H vessels play a role in the cou-pling of angiogenesis and osteogenesis in the formation of new bone and promoting bone regeneration at the defect site.In re-cent years,miRNA regulates hypoxia inducible factor 1α(HIF-1 α)/vascular endothelial growth factor(VEGF),Notch,plate-let-derived growth factor-BB(PDGF-BB),Wnt/glycogen syn-thase kinase-3 β(GSK3 β)to affect the migration,recruitment,proliferation and differentiation of endothelial cells(ECs)and osteoblast(OB),promote the coupling of H-type vessels and os-teoblasts to improve bone homeostasis,and then prevent and treat bone metabolic diseases.This article explains the role of miRNA in regulating H-type vascular osteogenic coupling to provide tar-gets and pathways for improving bone homeostasis.In addition,the active ingredients of traditional Chinese medicine affect the differential expression of miRNA to promote H-type angiogenesis and provide strategies for clinical prevention and treatment of bone metabolic diseases.

This study investigated the epidemic status of H3N2 influenza virus and the genetic evolution characteristics of hemagglutinin(HA)and neuraminidase(NA)of H3N2 subtype influenza viruses isolated in Shandong Province during 2023-2024,to understand their compatibility with vaccine strains and drug resistance status.A total of 25 H3N2 subtype influenza virus strains were randomly selected from the strains isolated by the influenza surveillance network laboratory.The HA and NA genes were sequenced with the vaccine strains recommended by the WHO as a reference.Monitoring of sensitivity to oseltamivir and zanamivir was conducted through neuraminidase inhibition experiments.The H3N2 influenza viruses in Shandong Province belonged to the 3C.2a1b.2a.2a.3a.1 clade.Nucleotide sequence analysis revealed that the HA1 and NA genes were closely related to the WHO-recommended vaccine strain A/Darwin/9/2021 for the current season,with homology rates of 97.8%-98.2%and 98.9%-99.3%,respectively.Amino acid sequence analysis indicated 22 amino acid sequence variations in the HA1 protein,and antigenic drift was detected in 8 strains.A glycosylation site was added at position 94 of the HA protein in all 25 strains.Variations occurred in the NA antigenic determinants of some strains.Neuraminidase inhibition experiments indicated that all tested influenza viruses were sensitive to oseltamivir and zanamivir.Some differences in HA and NA proteins were observed between the monitored strains and vaccine strains.Continued monitoring of the molecular evolution characteristics of influenza viruses is necessary to understand the risk of influenza outbreaks,and their effects on the effectiveness of influenza vaccines and therapeutic drugs.