ObjectiveTo observe the effects of Danggui Shaoyaosan on macrophage polarization and renal inflammation in db/db mice with diabetic kidney disease （DKD）， and to explore its renal protective effects and underlying mechanisms. MethodsEight db/m mice were assigned to the normal group， and forty db/db mice were randomly divided into a model group， low-， medium-， and high-dose Danggui Shaoyaosan groups （8.39， 16.77， 33.54 g·kg^-1）， and an irbesartan group （0.025 g·kg^-1）. All mice were administered treatment by gavage for 12 consecutive weeks. General conditions of the mice were observed during the intervention. At the end of the 12-week intervention， 24-h urine samples were collected using metabolic cages， after which the mice were anesthetized for sample collection. Blood was collected by enucleation and centrifuged to obtain serum for the determination of glycated serum protein （GSP）， serum creatinine （SCr）， blood urea nitrogen （BUN）， total cholesterol （TC）， and triglycerides （TG）. The urinary albumin-to-creatinine ratio （UACR） was measured. Renal pathological changes were observed using hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum tumor necrosis factor-α （TNF-α）， interleukin-10 （IL-10）， and monocyte chemoattractant protein-1 （MCP-1） levels. Immunofluorescence （IF） was performed to detect F4/80 expression in renal tissue， and immunohistochemistry （IHC） was used to assess CD206 expression. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA expression of TNF-α， IL-10， inducible nitric oxide synthase （iNOS）， and arginase-1 （Arg-1）. Western blot analysis was used to detect the protein expression of iNOS， Arg-1， CD86， and CD206 in renal tissue. ResultsCompared with the normal group， the model group showed increased levels of GSP， UACR， SCr， BUN， TC， and TG， elevated levels of the inflammatory factor TNF-α and the chemokine MCP-1， and decreased IL-10 levels （P<0.01）. Pathological examination revealed glomerular hypertrophy， mesangial cell proliferation with marked mesangial expansion， inflammatory cell infiltration， vacuolar degeneration of renal tubular epithelial cells， prominent glycogen deposition， and increased collagen fiber deposition. In addition， relative F4/80 fluorescence intensity was enhanced， CD206 expression in the glomeruli and renal interstitium was reduced， and TNF-α and iNOS mRNA expression was increased. IL-10 and Arg-1 mRNA expression was decreased， iNOS and CD86 protein expression was increased， and Arg-1 and CD206 protein expression was decreased （P<0.05， P<0.01）. Compared with the model group， the Danggui Shaoyaosan groups and the irbesartan group showed decreased levels of GSP， UACR， SCr， BUN， TC， and TG， reduced serum TNF-α and MCP-1 levels， and increased IL-10 levels. Renal pathological damage was improved to varying degrees. Relative F4/80 fluorescence intensity was reduced， CD206 expression in the glomeruli and renal interstitium was increased， and TNF-α and iNOS mRNA expression was decreased. IL-10 and Arg-1 mRNA expression was increased， iNOS and CD86 protein expression was reduced， and Arg-1 and CD206 protein expression was increased （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan can improve renal function and alleviate renal pathological damage in db/db mice. Its mechanism may be related to inhibiting M1 pro-inflammatory macrophage polarization， promoting M2 anti-inflammatory macrophage polarization， reducing inflammatory responses， delaying the progression of renal fibrosis， improving renal pathological injury， and thereby exerting renal protective effects.

ObjectiveTo investigate the effect of Danggui Shaoyaosan on the expression of Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 （TLR4/NF-κB p65/NLRP3） signaling pathway in the renal tissues of db/db mice with spontaneous diabetes， and to explore the potential mechanism by which Danggui Shaoyaosan alleviates inflammation in diabetic kidney disease （DKD）. MethodsThirty db/db mice were divided into five groups： A model group， Danggui Shaoyaosan low- （16.77 g·kg^-1·d^-1）， medium- （33.54 g·kg^-1·d^-1）， and high-dose （67.08 g·kg^-1·d^-1） intervention groups， as well as an irbesartan group （0.025 g·kg^-1·d^-1） by the random number table method， with 6 mice in each group. Additionally， 6 db/m mice were assigned to the normal group. After 8 weeks of intervention， the following parameters were determined by corresponding methods： body weight， fasting blood glucose （FBG）， 24-hour urinary protein （24 h-UTP）， and serum creatinine （SCr） levels， renal histopathological analysis by hematoxylin-eosin （HE） staining， Masson staining， and periodic acid-Schiff （PAS） staining， the protein and mRNA expression levels of TLR4， NF-κB p65， NLRP3， tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and interleukin-18 （IL-18） by Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR）， as well as TLR4， NF-κB p65， and NLRP3 protein expression in renal tissues by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group exhibited increased body weight， FBG， 24 h-UTP， and SCr levels （P<0.05）； disordered renal structure， thickened basement membrane， and interstitial inflammatory cell infiltration， elevated TLR4， NF-κB p65， NLRP3， TNF-α， IL-1β， IL-6， and IL-18 expression； as well as decreased IL-10 expression （P<0.05）. Compared with the model group， these pathological changes and biochemical abnormalities were reversed in the medicine intervention groups to varying degrees （P<0.05）. ConclusionDanggui Shaoyaosan may delay DKD progression by alleviating renal inflammatory response and reducing urinary protein excretion via modulating the TLR4/NF-κB p65/NLRP3 signaling pathway.

As the core vehicle for preserving and transmitting traditional Chinese medicine（TCM） academic thought and clinical experience， the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine， this study conducted a comprehensive analysis of critical challenges， including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic， encompassing three dimensions of authenticity and standardization， characteristics and advantages， application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment， while aligning with modern scientific research standards， achieving a balance between individualized TCM experience and standardized evaluation. Concurrently， this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases， contributing significantly to the inheritance of TCM knowledge， evidence-based practice， and the reform of talent evaluation mechanisms.

Background/Aims: Biliary tract cancer (BTC) frequently harbors KRAS mutations, which are associated with resistance to traditional treatment and a poor prognosis. Synthetic lethality (SL) strategy may provide other targets of KRAS. Therefore, we aim to identify and validate potential therapeutic targets of KRAS for the treatment of BTC via SL. Methods: The dependency (DepMap) projects were used to predict the synthetic lethal gene of KRAS. FDA-approved anticancer drug library was applied to screen potential drugs effective against KRAS-mutant BTC. Furthermore, the synthetic lethal effects or corresponding mechanisms of potential genes and drugs on BTC were investigated using KRAS-mutant and KRAS-wild type BTC cell lines, patient-derived xenografts (PDX), and KRAS oncogene-driven tumor models, as well as other KRAS-mutant cancer cell lines. Results: Initially, we discovered that the loss of GATA2 reduced the viability of KRAS-mutant but not KRAS-wild-type BTC. Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting interleukin-1β (IL-1β) in KRAS-mutant BTC. Mechanistically, GATA2 specifically enhanced the transcription of IL-1β to promote NF-κB signaling in KRAS-mutant BTC. IL-1β inhibition phenocopied GATA2 deficiency, leading to reduced KRAS-mutant BTC viability. These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. Conclusions In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Definitive chemoradiotherapy (dCRT) has become a cornerstone in the treatment of locally advanced esophageal cancer; however, local control remains suboptimal, and persistent lesions or locoregional recurrences after treatment are not uncommon. For patients without distant metastases but with local failure, whether surgical intervention can still offer curative potential remains a major clinical dilemma. Salvage esophagectomy (SE) offers potential long-term survival for selected patients, but this procedure is performed in the context of severe fibrosis, impaired local blood supply, and obscured anatomical planes following chemoradiotherapy, resulting in significantly higher perioperative risk compared to primary esophagectomy. Consequently, controversies exist regarding patient selection, preoperative restaging, choice of surgical approach, extent of lymphadenectomy, gastrointestinal reconstruction, and perioperative management. In recent years, with the refinement of restaging modalities such as PET/CT, the accumulation of experience in high-volume centers, and emerging evidence from clinical studies, the clinical role of SE has gradually shifted from a "high-risk salvage measure" to a "selective curative strategy aimed at achieving long-term survival in carefully selected patients". Nevertheless, standardized guidelines for patient selection, technical approaches, and perioperative management are still lacking. Based on current evidence and clinical experience, experts organized by the Integrated Esophageal Cancer Committee of Chinese Anti-Cancer Association systematically reviewed key issues regarding SE, including its definition, indications, preoperative evaluation, choice of surgical approach, lymphadenectomy, gastrointestinal reconstruction, and perioperative management, and formulated a Chinese expert consensus. This consensus aims to provide guidance for standardized assessment, appropriate referral, individualized surgical decision-making, and optimized perioperative management of patients with locoregional failure after dCRT. Ultimately, this will increase the likelihood of R0 resection, reduce the risk of severe complications, and promote the safer, more judicious, and standardized implementation of SE in high-risk scenarios.

Clonorchis sinensis primarily lives in the host liver and biliary system, leading to serious health issues, such as hepatobiliary lesions and cholangiocarcinoma. Establishment of rapid, sensitive and specific tools is of great significance for early diagnosis and management of clonorchiasis. Recently, molecular biological techniques have been widely used for detection of C. sinensis infections. This review summarizes the advances in the major molecular assays for detection of C. sinensis infections in intermediate and definite hosts, including PCR, loop-mediated isothermal amplification, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins system, and high-throughput sequencing, and summarizes the characteristics and application prospects of these assays, so as to provide precision detection and management of C. sinensis infection.

ObjectiveTo investigate the mRNA expression profile and clinical significance of the RAB24 gene in hepatocellular carcinoma （HCC） based on multi-source database including The Cancer Genome Atlas （TCGA） and clinical cohort validation. MethodsData from TCGA （n=424） were utilized to evaluate the prognostic value of RAB24 expression via Kaplan-Meier analysis and Cox regression models. An independent clinical cohort comprising 90 HCC and 30 paracancerous tissues was established to validate protein expression and histopathological features through immunohistochemistry （IHC） and routine histological staining. The TIMER database was employed to analyze the association between RAB24 and the tumor microenvironment （TME）. Furthermore， integrated with LinkedOmics， GSEA and GSVA algorithms were used to quantitatively characterize the core molecular pathways regulated by RAB24. ResultsThe mRNA expression level of RAB24 in HCC was significantly higher than that in non-tumor liver tissues （P<0.05）. Kaplan-Meier analysis revealed that the overall survival （OS） of patients in the RAB24 low-expression group was significantly longer compared to the high-expression group （HR=1.570， Log-rank P=0.01）. Cox proportional hazards regression analysis demonstrated that RAB24 expression （HR=1.480， P=0.028）， T stage （HR=2.949， P<0.001）， M stage （HR=4.077， P=0.017）， and tumor residual status （HR=2.317， P<0.001） were independent prognostic factors for HCC. RAB24 expression was highly correlated with alpha-fetoprotein （AFP） levels and immune infiltration levels （P<0.01）， and showed a significant， low-level positive correlation with the TP53 gene （Rho=0.31， P<0.01）. Quantitative analysis of the RAB24 protein in clinical samples validated that RAB24 expression in HCC tissues was significantly elevated compared to non-tumor liver tissues （P<0.05）. TIMER analysis confirmed that RAB24 expression was highly associated with the infiltration of multiple immune cells （such as B cells and NK cells）， as well as stromal and tumor purity scores in tumor tissues （P<0.01）. GSEA/GSVA enrichment revealed that the P53， MYC， and mTORC1 signaling pathways were activated in the RAB24 high-expression group； correlation analysis confirmed that the RAB24 expression level exhibited a significant， low-level positive correlation with the ribosome pathway activity score （r=0.23， P<0.01）. ConclusionsThe RAB24 gene， as a poor prognostic factor for HCC patients， is a potential biomarker for HCC diagnosis， treatment and prognosis. The study is expected to lay a theoretical foundation for the precise diagnosis and treatment of clinical HCC.

OBJECTIVE To explore the mechanism of Yiqi yangyin huazhuo tongluo formula in ameliorating diabetic kidney disease （DKD） based on the gut microbiota-lipopolysaccharide （LPS）/Caspase-11/gasdermin D （GSDMD） pathway.METHODS A DKD mouse model was established by high-fat and high-sugar diet combined with intraperitoneal injection of low-dose streptozotocin. The successfully modeled mice were randomly divided into model group， metformin group （positive control， 200 mg/kg） and Yiqi yangyin huazhuo tongluo formula group （32.4 g/kg， calculated as crude drug dosage）， with 10 mice in each group； another 10 mice were set as the control group. Mice were intragastrically administered with corresponding drug solutions or normal saline once a day for 8 consecutive weeks. After the last administration， serum glycolipid metabolism indicators and urinary renal function indicators of mice were determined； the pathological and morphological changes of renal and colonic tissues were observed； LPS contents in renal tissues， colonic contents and serum were detected. 16S rRNA high-throughput sequencing was performed for gut microbiota analysis of colonic contents. The protein expressions of Occludin and zonula occludens-1 （ZO-1） in colonic tissues as well as Caspase-11 and GSDMD in renal tissues were detected.RESULTS Compared with the control group， the model group exhibited significantly elevated levels of serum fasting blood glucose， triglyceride， total cholesterol， serum creatinine， blood urea nitrogen and microalbumin， LPS contents in each sample， as well as protein expressions of Caspase-11 and GSDMD in renal tissues （ P ＜0.05）. The protein expressions of ZO-1 and Occludin in colonic tissues， together with Chao1 and Ace indices of gut microbiota， were markedly decreased （ P ＜0.05）， and the ratio of Firmicutes to Bacteroidetes was abnormally increased. Obvious histopathological changes were observed in renal and colonic tissues； the percentage of PAS-positive area in kidney was markedly increased （ P ＜0.05）. Compared with the model group， the Yiqi yangyin huazhuo tongluo formula group showed remarkable reductions in glycolipid metabolism and renal function-related indicators（except total cholesterol）， LPS contents in various samples， and renal protein expressions of Caspase-11 and GSDMD （ P ＜0.05）. The protein expression level of ZO-1 in colonic tissues and the Ace index of gut microbiota were significantly increased （ P ＜0.05）， and the relative abundance of beneficial genera including Bifidobacterium ， Faecalibaculum and Akkermansia in the gut microbiota was elevated.CONCLUSIONS The mechanism by which Yiqi yangyin huazhuo tongluo formula ameliorates DKD may be related to reshaping gut microbiota， repairing intestinal mucosal barrier， reducing LPS translocation into blood， and further inhibiting Caspase-11/GSDMD-mediated pyroptosis in kidney.

ObjectiveTo analyze the pharmacodynamic activity of Bupleuri Radix processed with Trionyx sinensis blood in the treatment of Yin deficiency and study the spectrum-effect relationship of this medicine. MethodsHigh performance liquid chromatography was employed to establish the fingerprints of 15 batches of Bupleuri Radix processed with Trionyx sinensis blood， and the similarity was evaluated according to the SOP of Similarity Evaluation System of Chromatographic Fingerprint of TCM （version 2012）. A mouse model of Yin deficiency induced by thyroxine was established. The relationship between the active components and the effect on Yin deficiency was explored by grey correlation analysis and partial least squares method based on the changes in the serum levels of triiodothyronine （T3）， thyroxine （T4）， cyclic adenosine phosphate （cAMP）， and cyclic guanosine phosphate （cGMP）. The components screened out based on the spectrum-effect relationship were used for retrieval of the targets from the Traditional Chinese Medicine Systems Pharmacology and Analysis Database （TCMSP）， The Encyclopedia of Traditional Chinese Medicine （ETCM）， and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Furthermore， the Online Mendelian Inheritance in Man （OMIM）， GeneCards， TTD， DisGeNET， and Drugbank were employed to establish the active component-target against Yin deficiency network of Bupleuri Radix processed with Trionyx sinensis blood. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were carried out for the core targets. Real-time PCR was conducted to verify the predicted key pathways and mechanisms. ResultsThe fingerprints of the 15 batches of Bupleuri Radix processed with Trionyx sinensis blood showed the similarities of 0.976-0.999 with the control fingerprint. Compared with the model group， the drug administration group showed elevated levels of T3 and T4 and lowered levels of cAMP， cGMP and cAMP/cGMP. The results of grey correlation analysis showed that active components in terms of the correlations followed the trend of saikosaponin B₁ > saikosaponin B₂ > saikosaponin C > saikosaponin D > saikosaponin A. The partial least squares analysis showed that saikosaponins A， D， B₁， and B₂ had higher VIP values. Network pharmacology predicted a total of 30 common targets， which were enriched in 276 GO terns and 115 KEGG pathways. The results of Real-time PCR showed that the model group had lower mRNA levels of Caspase-9， kinase insert domain receptor （KDR）， and mammalian target of rapamycin （mTOR） and higher mRNA level of mouse double minute 2 homolog （MDM2） than the blank group and the drug administration group. ConclusionBupleuri Radix processed with Trionyx sinensis blood has therapeutic effect on Yin deficiency syndrome， which provides a new idea for studying Bupleuri Radix processed with Trionyx sinensis blood.

Objective To explore the pathogenesis and prognostic factors of liposarcoma in the head and neck region, and simultaneously analyze the efficacy of different treatment regimens. Methods A retrospective analysis was performed on all patients with primary untreated head and neck liposarcoma who were diagnosed and underwent surgical treatment at our hospital from January 2008 to January 2024. All patients were monitored during follow-up, and their prognoses were analyzed using SPSS software. Results A total of 30 patients were included in the study. Liposarcoma accounted for up to 60% of the cases in the orbit, while the remaining liposarcomas were primarily located in various interspaces of the neck. Dedifferentiated liposarcoma was the most common type, comprising 33%, while myxoid pleomorphic liposarcoma was the rarest at 4%. The tumor pathological type (P<0.001) and Ki67 (P=0.014) significantly affected the tumor control rate. However, an analysis of disease-specific survival rates revealed no significant differences across various factors (all P>0.05). Conclusion The prognosis of head and neck liposarcoma is better compared to that of liposarcomas in other parts of the body. However, myxoid pleomorphic liposarcoma, pleomorphic fat sarcoma, and high Ki67 levels are indicators of poor prognosis. Additionally, postoperative adjuvant radiotherapy does not significantly enhance disease-specific survival rates.