Hepatocellular carcinoma （HCC） is a common malignant tumor with a high fatality rate worldwide， with limited overall survival benefits and pronounced drug resistance issues， highlighting the urgent need for novel sensitization strategies and patient stratification systems. Ferroptosis， as an iron-dependent form of lipid peroxidation-driven cell death， is closely associated with tumor treatment responses. In addition to the classic glutathione peroxidase 4 （GPX4）/glutathione （GSH） pathway， the ferroptosis suppressor protein 1 （FSP1）-coenzyme Q10 （CoQ10） pathways and the dihydroorotate dehydrogenase （DHODH） pathway are two newly identified anti-ferroptosis pathways that function at the plasma membrane and mitochondria， respectively， and determine cellular sensitivity to ferroptosis in synergy with GPX4. This article systematically reviews the mechanism of action of the FSP1-CoQ10 and DHODH pathways in HCC and related research advances， proposes related therapeutic strategies， and look forward to its clinical translation and application prospects.

During routine Good Manufacturing Practice(GMP) compliance supervision, periodic inspections based on risk control concepts have revealed gaps between the current practices of biologics manufacturers in Jilin Province and the latest domestic and international regulatory standards. These gaps span multiple areas, including facility and equipment design for aseptic product manufacturing, airflow pattern control, cleaning and disinfection practices, environmental monitoring, aseptic process simulation, and personnel gowning procedures. This paper compiles and analyzes these identified issues. Considering the inherent tendency of biological product components to support microbial growth, and based on recent regulatory updates alongside a statistical analysis of aseptic manufacturing deficiencies observed during GMP compliance inspections in Jilin's biologics sector, this paper discusses the future direction for improving aseptic assurance levels. The aim is to provide theoretical support for both future regulatory efforts and the enhancement of aseptic assurance capabilities within enterprises.

The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

[摘 要] 目的：探究西贝素通过调控Cyclin D1介导的CDK4/6-Rb-E2F1信号轴对人胃腺癌细胞（AGS）的增殖抑制效果及其分子机制。方法：利用不同浓度的西贝素处理AGS和人正常胃黏膜上皮细胞（GES-1），通过CCK-8检测和结晶紫染色实验确定西贝素的最适抑制剂量和作用时间；采用划痕实验和Transwell迁移实验与侵袭实验检测西贝素对AGS细胞迁移与侵袭能力的影响；利用流式细胞术和WB检测西贝素对AGS细胞周期及细胞周期相关蛋白表达的影响；利用质粒过表达Cyclin D1，并通过WB检测、结晶紫染色实验、划痕实验和Transwell迁移实验与侵袭实验进一步明确西贝素的抑制机制；构建AGS移植瘤裸鼠模型，采用免疫荧光染色法和免疫组化检测Cyclin D1、CDK4、CDK6、Rb、p-Rb、E2F1的表达水平。结果：与对照组相比，西贝素药物浓度为100 μg/mL时，对GES-1细胞的增殖无影响（P > 0.05），但能够显著性抑制AGS细胞增殖、迁移和侵袭能力（P < 0.01），并诱导AGS细胞周期G0/G1期阻滞，显著抑制周期相关蛋白Cyclin D1、CDK4、CDK6、p-Rb、E2F1的表达水平（P < 0.05或P < 0.01）；Cyclin D1过表达能够显著降低西贝素对AGS细胞的抑制效果（P < 0.05或P < 0.01）；荷瘤裸鼠实验结果显示，西贝素能够抑制AGS移植瘤的增殖，影响肿瘤组织中Cyclin D1、CDK4、CDK6、p-Rb、E2F1的表达（P < 0.01）。结论：西贝素可能通过下调Cyclin D1介导的CDK4/6-Rb-E2F1信号轴活化抑制AGS增殖。

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Differentiated liposarcoma is a rare connective tissue malignancy in adults that mostly occurs in the extremities and retroperitoneum, with a tendency to aggressiveness and recurrence, and the ten-year survival rate of about 10%. Clinically, dedifferentiated liposarcoma of the pharynx has been reported to be rare abroad and only one case has been reported in China. Clinical symptoms are mainly foreign body sensation in the pharynx, which can be easily misdiagnosed as benign tumors. Pathological diagnosis is the main examination tool for this kind of disease, and immunohistochemistry and FISH test can help to differentiate it from other tumors. This article presents a case of a male patient with dedifferentiated liposarcoma of the hypopharynx, who had a foreign body sensation in the pharynx for more than 1 month, and underwent supported laryngoscopic pharyngeal lesion resection after completing the preoperative relevant examinations and postoperative radiation therapy, with postoperative pathology returned as dedifferentiated liposarcoma. The present postoperative follow-up was 12 months without recurrence. Therefore, accurate diagnosis and timely treatment are extremely important for the prognosis of this disease.
Humans ; Male ; Liposarcoma/diagnosis* ; Hypopharyngeal Neoplasms/diagnosis* ; Middle Aged ; Hypopharynx ; Adult

Immunotherapy has emerged as a revolutionary approach to treat immune-related diseases. Dendritic cells (DCs) play a pivotal role in orchestrating immune responses, making them an attractive target for immunotherapeutic interventions. Modulation of gene expression in DCs using genome editing techniques, such as the CRISPR-Cas system, is important for regulating DC functions. However, the precise delivery of CRISPR-based therapies to DCs has posed a significant challenge. While lipid nanoparticles (LNPs) have been extensively studied for gene editing in tumor cells, their potential application in DCs has remained relatively unexplored. This study investigates the important role of cholesterol in regulating the efficiency of BAMEA-O16B lipid-assisted nanoparticles (BLANs) as carriers of CRISPR/Cas9 for gene editing in DCs. Remarkably, BLANs with low cholesterol density exhibit exceptional mRNA uptake, improved endosomal escape, and efficient single-guide RNA release capabilities. Administration of BLAN_mCas9/gPD-L1 results in substantial PD-L1 gene knockout in conventional dendritic cells (cDCs), accompanied by heightened cDC1 activation, T cell stimulation, and significant suppression of tumor growth. The study underscores the pivotal role of cholesterol density within LNPs, revealing potent influence on gene editing efficacy within DCs. This strategy holds immense promise for the field of cancer immunotherapy, offering a novel avenue for treating immune-related diseases.

Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 in situ hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of Rfx1 in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression.

In recent decades, the prevalence of hyperuricemia and gout has increased dramatically due to lifestyle changes. The drugs currently recommended for hyperuricemia are associated with adverse reactions that limit their clinical use. In this study, we report that berberine (BBR) is an effective drug candidate for the treatment of hyperuricemia, with its mechanism potentially involving the modulation of gut microbiota and its metabolite, succinic acid. BBR has demonstrated good therapeutic effects in both acute and chronic animal models of hyperuricemia. In a clinical trial, oral administration of BBR for 6 months reduced blood uric acid levels in 22 participants by modulating the gut microbiota, which led to an increase in the abundance of Bacteroides and a decrease in Clostridium sensu stricto_1. Furthermore, Bacteroides fragilis was transplanted into ICR mice, and the results showed that Bacteroides fragilis exerted a therapeutic effect on uric acid similar to that of BBR. Notably, succinic acid, a metabolite of Bacteroides, significantly reduced uric acid levels. Subsequent cell and animal experiments revealed that the intestinal metabolite, succinic acid, regulated the upstream uric acid synthesis pathway in the liver by inhibiting adenosine monophosphate deaminase 2 (AMPD2), an enzyme responsible for converting adenosine monophosphate (AMP) to inosine monophosphate (IMP). This inhibition resulted in a decrease in IMP levels and an increase in phosphate levels. The reduction in IMP led to a decreased downstream production of hypoxanthine, xanthine, and uric acid. BBR also demonstrated excellent renoprotective effects, improving nephropathy associated with hyperuricemia. In summary, BBR has the potential to be an effective treatment for hyperuricemia through the gut-liver axis.

Necroptosis, a form of programmed cell death, initiates a series of biological responses and further culminates in necroinflammatory processes, consequently limiting the efficacy of cytokine antagonists in treating inflammatory diseases. To address this issue, DNAzyme R3-Dz specifically targeting receptor-interacting protein kinase 3 (RIP3) mRNA, a necrosome component, has been successfully developed and studied to elucidate the mechanism in cleaving its target mRNA. Then a polyamidoamine (PAMAM) derivative was constructed through the modification of nucleobase analog (termed AP) to achieve the R3-Dz delivery to macrophages. The AP/R3-Dz nanoparticles effectively downregulated the RIP3 expression, leading to subsequent decrease in the levels of reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs), ultimately inhibiting the necroinflammatory processes mediated by the NOD-like receptor family pyrin domain-containing 3 (NLRP3). Finally, AP/R3-Dz nanoparticles and their combination with the NLRP3 inhibitor MCC950 suppressed the necrotic phenotype and ameliorated the disease progression in diverse models, including gouty arthritis, autoimmune hepatitis and rheumatoid arthritis. In summary, the AP/R3-Dz nanoparticles in combination with MCC950 have been demonstrated to achieve the intervention in necroptosis and inflammation by dual disruption of the intricate feedback loop of necroinflammation and thus have promising potential in the treatment of inflammatory diseases.