ObjectiveTo investigate the mechanism by which adrenoceptor alpha 2A (Adra2a) regulates lipopolysaccharide (LPS)-induced inflammation in primary hepatocytes from lipopolysaccharide-binding protein (LBP) knockout mice (Lbp^-/-). MethodsPrimary hepatocytes from C57BL/6J and Lbp^-/- mice were isolated using a two-step perfusion method. An in vitro inflammatory model was established by LPS stimulation, and an in vivo inflammatory mouse model was established by intraperitoneal injection of LPS. The in vitro experiments were grouped as follows: Control group, LPS group, BRL+LPS group, OE-NC+LPS group, and OE-Adra2a+LPS group. The Control group served as the blank control. The LPS group involved stimulating primary hepatocytes with LPS. The BRL+LPS group involved pretreating primary hepatocytes with BRL-44408 maleate followed by LPS stimulation. The OE-NC+LPS group involved transfecting primary hepatocytes with an empty vector followed by LPS stimulation. The OE-Adra2a+LPS group involved transfecting primary hepatocytes with a lentivirus overexpressing Adra2a, followed by LPS stimulation. The in vivo experimental groups were divided into Control', LPS', BRL+LPS', OE-NC+LPS', and OE-Adra2a+LPS' groups. The Control' group served as the blank control. The LPS' group received intraperitoneal injection of LPS. The BRL+LPS' group received intraperitoneal injection of BRL-44408 maleate for pretreatment, followed by LPS injection. The OE-NC+LPS' group received intraperitoneal injection of empty vector for pretreatment, followed by LPS injection. The OE-Adra2a+LPS' group received intraperitoneal injection of a lentivirus overexpressing Adra2a for pretreatment, followed by LPS injection. Cell viability after Adra2a inhibition and overexpression was assessed via the Cell Counting Kit-8 (CCK-8) assay. RT-qPCR measured changes in gene expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) after Adra2a inhibition and overexpression. Western blotting was performed to detect Adra2a protein expression and phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase, and c-Jun N-terminal kinase (JNK) following LPS stimulation. ResultsIn vitro experiments revealed that LPS stimulation significantly decreased Adra2a protein expression in primary hepatocytes from C57BL/6J mice compared to the Control group (P<0.05), whereas it increased in primary hepatocytes from Lbp^-/- mice (P<0.001). Compared to the LPS group, the BRL+LPS group exhibited significantly increased cell viability (P<0.01), reduced TNF-α, IL-6, and IL-1β gene transcription levels (P<0.01, P<0.001, P<0.001), and decreased phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.01, P<0.001, P<0.001). Compared with the OE-NC+LPS group, the OE-Adra2a+LPS group showed significantly decreased cell viability (P<0.001), increased gene transcription levels of TNF-α, IL-6, and IL-1β genes (P<0.001, P<0.01, P<0.001), and elevated phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.001). In vivo experiments showed that, compared with the LPS' group, the BRL+LPS' group exhibited significantly reduced phosphorylation levels of MAPK signaling pathway-related proteins ERK1/2, p38, and JNK (P<0.001, P<0.01, P<0.01). In the OE-Adra2a+LPS' group, the phosphorylation levels of ERK1/2, p38, and JNK were significantly elevated compared to the OE-NC+LPS' group (P<0.01, P<0.001, P<0.01). ConclusionLPS stimulation can cause a significant increase in Adra2a protein expression in primary hepatocytes of Lbp^-/- mice. Adra2a protein can regulate the level of LPS-induced inflammation in primary hepatocytes of Lbp^-/- mice through the MAPK signaling pathway.

In the context of the development of transplant oncology,it is of great clinical significance to find a drug with both antitumor and immunosuppressive effects for liver transplantation patients with hepatocellular carcinoma(HCC).The antitumor effect of ginkgolic acid(GA)has been confirmed,and some studies suggest that GA may also have an immunosuppressive effect.The immunosuppressive effect of GA was evaluated by histopathology,T-cell subpopulation,and cytokine detection in rat liver transplantation and mouse cardiac transplantation models,and transcriptomic and metabolomic analysis was used to explore the underlying mechanism of the GA immunosuppressive effect.Metabolites,activation,and ferroptosis markers of CD8+T cells were detected in vivo and in vitro.Based on rat liver transplantation and mouse cardiac transplantation models,the immunosuppressive effect of GA was first confirmed by histopathology,T-cell subpopulation,and cytokine detection.In the mouse cardiac transplantation model,transcriptomics combined with metabolomics demonstrated for the first time that GA inhibited lactate dehydrogenase A(LDHA)expression and pyruvate metabolism in CD8+T cells.It was confirmed in vivo and in vitro that GA inhibited pyruvate metabolism of CD8+T cells through LDHA,inhibiting their activation and inducing ferroptosis.Over-expression of LDHA partially reversed the effect of GA on the metabolism,activation,and ferroptosis of CD8+T cells in vitro.GA mediates metabolic reprogramming through LDHA to inhibit the activation and induce ferroptosis of CD8+T cells to exert an immunosuppressive effect,which lays an experimental foundation for the future clinical application of its immunosuppressive effect.

Objective:To investigate the role of the IgG subtypes (IgG1 and IgG2a) in anti-glycoprotein (GP) Ⅰbα antibody-induced platelet clearance.Methods:Venous blood was collected from healthy volunteers, and platelets were separated. The phagocytosis of human platelets by human acute monocytic leukemia cells (THP-1 cells) induced by different anti-GPⅠbα antibodies (AN51, AK2, HIP1, TM60, VM16d, WM23, and SZ2) was detected by flow cytometry. The effects of the AN51 full-length antibody, F (ab') 2, and Fab fragments on platelet phagocytosis by THP-1 cells were detected by flow cytometry. Then, the Fc blocking antibody 2.4G2 and normal rat IgG2a or IgG1 were injected into C57BL/6J mice via the posterior ocular vein, and their effects on platelet reduction induced by R300 were detected by a hematology analyzer. Results:Compared with IgG1, the IgG2a subtype of anti-GPⅠbα antibodies induced the phagocytosis of platelets by THP-1 cells in vitro ( P<0.05). In contrast to the AN51 full-length antibody, neither AN51 F (ab') 2 nor the Fab fragment could induce THP-1 cells to phagocytose platelets ( P<0.05). Compared with the control group, anti-mouse GPⅠbα R300-induced thrombocytopenia in mice was reduced at 2, 4, and 6 h after the injection of Fc blocking antibody 2.4G2 ( P<0.05). Similarly, R300-induced thrombocytopenia in mice was reduced at 2, 4, and 6 h after the injection of rat IgG2a ( P<0.05) . Conclusion:IgG2a plays an important role in anti-GPⅠbα-induced clearance.

ObjectiveThis paper aims to systematically collect and organize ancient and modern clauses and studies containing Xieqingwan， excavate and analyze the key information of Xieqingwan， and provide a reference for facilitating the development of the classic formula Xieqingwan. MethodsThe composition， dosage， decocting methods， usage， and other key information of Xieqingwan in ancient traditional Chinese medicine books were collected and analyzed by means of literature research and metrological methods. The modern clinical application of Xieqingwan was summarized. ResultsA total of 42 pieces of effective data involving 32 ancient traditional Chinese medicine books were collected. Xieqingwan was first recorded in Xiaoer Yaozheng Zhijue. The drug origin of this formula is basically clear in the ancient traditional Chinese medicine books. The modern drug usage and decocting method were as follows： Angelicae Sinensis Radix， Gentianae Radix et Rhizoma， Chuanxiong Rhizoma， Gardenia seeds， Radix et Rhizoma Rhei， Notopterygii Rhizoma et Radix， and Saposhnikoviae Radix were grounded to fine powder， decocted with honey， and finally formed into pills with the size of a chicken head （1.5 g）. It was suggested that half a pill or one pill were taken for one dose with warm Lophatheri decoction and sugar. The indications and clinical application had developed from the recordings in Xiaoer Yaozheng Zhijue and evolved from pediatrics to ophthalmic otolaryngology， neurology， dermatology， digestion， and respiratory diseases. The main pathogenesis of these diseases is heat in the liver meridian and is treated. The effect of Xieqingwan is "clearing away heat and toxicity， removing fire and relaxing the bowels， and dispersing swelling and relieving pain". It is recommended to use the corresponding preparation methods in the 2020 Edition of Pharmacopoeia of the People's Republic of China. Modern clinical studies are centered around the clinical application of Xieqingwan， which is often modified and used in treating Tourette syndrome， herpes， febrile convulsion， sleepwalking， and insomnia. ConclusionThis paper conducts a thorough textual research of the key information of Xieqingwan， induces its historic evolution， and confirms its key information， so as to provide a reference for the future development of Xieqingwan.

In recent years， hyperuricemia （HUA） has shown a rapidly increasing incidence and tends to occur in increasingly young people， with a wide range of cardiac， renal， joint， and cancerous hazards and all-cause mortality associations. Western medicine treatment has limitations such as large liver and kidney damage， medication restriction， and easy recurrence. The intestine is the major extra-renal excretion pathway for uric acid （UA）， and the intestinal microecology can be regulated to promote UA degradation. It offers great potential to develop UA-lowering strategies that target the intestinal microecology， which are promising to provide safer and more effective therapeutic approaches. Traditional Chinese medicine （TCM） can treat HUA via multiple targets and multiple pathways from a holistic view， with low toxicity and side effects. Studies have shown that intestinal microecology is a crucial target for TCM in the treatment of HUA. However， its specific mechanism of action has not been fully elucidated. Focusing on the key role of intestinal microecology in HUA， this review explores the relationship between intestinal microecology and HUA in terms of intestinal flora， intestinal metabolites， intestinal UA transporters， and intestinal barriers. Furthermore， we summarize the research progress in TCM treatment of HUA by targeting the intestinal microecology， with the aim of providing references for the development of TCM intervention strategies for HUA and the direction of future research.

Primary liver cancer,particularly hepatocellular carcinoma,is one of the most common malignancies in China,and hepatectomy remains the primary curative treatment.However,the efficacy of hepatectomy is significantly limited due to the heterogeneity of liver cancer,its high recurrence rate,and the fact that most patients are diagnosed at advanced stages.In recent years,the development of precision medicine has brought new hope to liver cancer treatment,especially with notable advancements in preoperative assessment,systemic therapy,minimally invasive surgery,and personalized treatment strategies.Preoperative assessment,including imaging technologies such as three-dimensional visualization and molecular imaging,helps physicians accurately evaluate tumor characteristics and liver function,guiding the choice of treatment plan.The combined application of immunotherapy and targeted therapy has significantly improved survival rates for patients with advanced liver cancer.The strategy of combining systemic therapy with local treatment has provided new pathways for translational therapy,expanding the indications for hepatectomy.The optimal selection of patients based on tumor biological characteristics,especially molecular subtyping and liver function status,to maximize patient benefit still requires further exploration.The"seven-step"modular laparoscopic hepatectomy,by achieving scientific hepatectomy,demonstrates the clinical practice of maximizing patient benefit,further elucidating a multidisciplinary,personalized treatment model centered on surgical therapy.

Although the incidence of each individual type of rare tumor is relatively low, their cumulative impact affects a vast patient population, and their survival prognosis is significantly worse than that of common tumors. In recent years, China has made remarkable progress in clinical research on rare tumors, with a rapid increase in the number of studies and a diversified exploration of treatment modalities. However, clinical research on rare tumors still faces numerous challenges, such as uneven distribution of medical resources, the absence of a foundational registration system, and insufficient motivation for original research and development. Looking ahead, key measures including specialized development, a national collaborative group model, full utilization of real-world data, application of novel clinical research designs, and artificial intelligence technologies will strongly drive comprehensive advancements in China′s rare tumor prevention and treatment system.

Pancreatic acinar cell carcinoma (PACC) is a rare exocrine tumor of the pancreas with distinct clinical and pathological features. In recent years, advancements in molecular biology techniques have led to a deeper understanding of the molecular mechanisms underlying PACC. Progress in imaging, endoscopic, and molecular diagnostic technologies has improved the early detection rate of PACC. The primary treatment modalities for PACC include surgical resection, chemotherapy, targeted therapy and immunotherapy; however, the therapeutic efficacy still requires further improvement. This article reviews the current research status of PACC, covering its epidemiology, pathological characteristics, molecular alterations, diagnostic methods, and treatment strategies, and discusses the controversies and future directions in PACC research.

Objective:To summarize the clinical manifestations, genetic characteristics and diagnosis and treatment processes of ATP1A2 gene-related childhood neurological diseases presenting with hemiplegic migraine (HM) or epilepsy, and enhance the understanding of clinicians on the diseases related to this gene. Methods:A retrospective study was performed; data of 5 children with ATP1A2 gene variations admitted to Department of Neurology, Hunan Children's Hospital from April 2015 to June 2024 were collected, and their clinical characteristics were summarized. ATP1A2 gene variations were confirmed by whole exome sequencing on these 5 children's families using next-generation sequencing (NGS), and then, further validated by Sanger sequencing. A comprehensive literature search was performed through PubMed, CNKI, and Wanfang databases to summarize the disease spectrum associated with this gene. Results:Among the 5 pediatric patients, 3 exhibited HM phenotype (all presented with neurological symptoms of epilepsy/febrile seizures within the first year of life, followed by HM onset after intervals ranging from 3 years and 3 months to 7 years); 2 pediatric patients aligned with epilepsy phenotype, including one instance of drug-resistant focal-onset epileptic encephalopathy. These 5 pediatric patients carried de novo missense variants in the ATP1A2 gene, encompassing 5 distinct mutation sites. Notably, the c.1023C>G (p.Cys341Trp) and c.2458G>A (p.Ala820Thr) variants were not documented in ClinVar or HGMD databases, and were classified as likely pathogenic according to American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines. Literature review revealed that all reported ATP1A2 mutations in Chinese pediatric patients were missense variants, with c.2143G>C (p.Gly715Arg) being the most commonly prevalent (8/29, 27.6%). The predominant clinical manifestation was HM (22/29), characterized by hemiplegia, aphasia, fever, impaired consciousness, and convulsions (early transient neurological symptoms frequently manifested as febrile seizures [12/22, 54.4%]); additionally, alternating hemiplegia of childhood was noted in 4 pediatric patients and epilepsy in 3 pediatric patients. Conclusion:ATP1A2 gene variants can lead to neurological disorders such as HM and epilepsy, with varied severity at same phenotype; the missense variants c.1023C>G and c.2458G>A in the ATP1A2 gene expand the spectrum of ATP1A2 gene variants and may serve as genetic causes of epilepsy.

Objective:To investigate the effect and mechanism of ginkgo acid(GA)on hepatic fibrosis in rats.Methods:CCl4 and TAA were used to construct rat liver fibrosis model,and GA or combined ferroptosis inhibitor(Fer-1)was given to intervene.The liver tissue and serum of rats were obtained and histopathologically evaluated by HE,Masson and Sirius red staining,respecively.The expression of HA,LN,Ⅳ-C and PC-Ⅲ in serum were detected by Elisa and the expression of GPX4 and FTH1 were detected by Western blot.Results:HE staining showed that,com-pared with TAA and CCl4 groups,the fibrosis level of GA group was significantly decreased.The results of Masoon and Sirius red staining showed that compared with TAA and CCl4 groups,the rate of collagen fibers in liver of GA group was significantly decreased(P＜0.05).Elisa results showed that compared with TAA and CCl4 groups,the levels of HA,LN,Ⅳ-C and PC-Ⅲ in serum of rats in GA group were significantly decreased(P＜0.05).After the intervention of GA com-bined with Fer-1,Western blot results showed that compared with TAA and CCl4 groups,the expression of GPX4 and FTH1 in liver of rats in GA group were significantly increased(P＜0.05).Compared with GA group,GPX4 and FTH1 levels in Fer group were significantly decreased(P＜0.05);The histopathological results showed that compared with GA group,the rate of liver collagen fibers in Fer group was significantly increased(P＜0.05).Conclusion:GA has anti-hepatic fi-brosis effect,which is associated with inducing ferroptosis.