The key to the onset and progression of the functional impairments of orthopedic diseases is imba-lance of deficiency and excess， disharmony of movement and stillness， dislocation of sinews and bones， imbalance of rigidity and flexibility， and disharmony of body and spirit. Based on this， the "five views" treatment principle has been proposed for traditional Chinese medicine （TCM） orthopedic rehabilitation， which include the view of balancing deficiency and excess， combining movement and stillness， focusing on both sinews and bones， integrating rigidity and flexibility， and harmonizing body and spirit. Correspondingly， the "five views" collaborative rehabilitation clinical model is established， providing a reference for enhancing the systematization and targeting of TCM orthopedic rehabilitation.

Gout is a crystal-associated arthropathy caused by the deposition of monosodium urate crystals and is closely related to purine metabolic disorders and impaired uric acid excretion. It is clinically characterized by hyperuricemia， recurrent joint swelling and pain， and tophus formation. The disease course is divided into three stages： The hyperuricemia stage， acute attack stage， and chronic gouty arthritis stage. Modern medicine has reached a consensus on its pathology， but traditional Chinese medicine （TCM） lacks a systematic stage-specific understanding of gout pathogenesis and its underlying mechanisms， making it difficult to guide precise syndrome differentiation and treatment. By integrating classical TCM theory， clinical practice， and modern medical understanding， and drawing upon descriptions of Bi syndrome caused by endogenous dampness and turbidity in classical texts such as Huangdi Neijing·Ling Shu and Synopsis of the Golden Chamber， our team proposes the pathogenic concept of gout as ''endogenous dampness leading to Bi syndrome'' and the core pathogenesis of ''spleen deficiency with internal retention of dampness-turbidity''. We systematically elucidate the evolution of pathogenesis across different stages and corresponding therapeutic strategies. This study posits that metabolic byproducts such as urate fall under the category of ''endogenous pathogenic dampness-turbidity''. When genetic or dietary factors lead to metabolic abnormalities， it manifests as ''spleen deficiency with impaired transport and transformation''， resulting in ''internal retention of pathogenic dampness-turbidity''. When damp-turbidity stagnates in the blood vessels， serum uric acid levels rise. When it stagnates in the viscera and limbs， monosodium urate crystals deposit in the joints. Triggered by precipitating factors， this leads to gout attacks—the core pathological process of ''endogenous dampness leading to Bi syndrome''. Based on this theory， the stage-specific pathogenic characteristics of gout are proposed： The hyperuricemia stage is characterized by ''spleen deficiency with impaired transport and transformation， internal retention of pathogenic dampness-turbidity''， the acute attack stage is primarily marked by ''dampness-turbidity and static heat obstructing the limbs and joints''， while the chronic stage is defined by ''spleen deficiency with internal retention of pathogenic dampness-turbidity， intermingled with phlegm-stasis binding''. The treatment principle centers on ''strengthening the spleen and draining dampness'' throughout all stages. During the hyperuricemia stage， treatment focuses on ''strengthening the spleen， draining dampness， and eliminating turbidity''. In the acute attack stage， the treatment should "strengthen the spleen， drain dampness， clear heat， eliminate turbidity， alleviate swelling， and relieve pain''. In the chronic stage， the treatments emphasizes to ''strengthen the spleen， drain dampness， transform turbidity， clear heat， resolve phlegm， and activate blood circulation''. This approach has yielded favorable therapeutic outcomes in clinical practice. This theoretical system clarifies the nature of gout as ''spleen deficiency being the root， dampness-turbidity being the secondary manifestation'' and systematically analyzes its pathogenesis evolution process and characteristics. The constructed stage-based treatment protocol has been validated through clinical and basic research， providing systematic theoretical guidance and a practical framework for the precise TCM management of gout， thereby promoting the modernization of TCM pathogenesis theory related to gout.

ObjectiveBased on the clinical characteristics of chronic gouty arthritis （CGA） in both traditional Chinese and western medicine， this study aims to systematically evaluate the clinical concordance of existing CGA animal models， providing recommendations for establishing animal models that align with the pathological characteristics of CGA and the manifestations of traditional Chinese medicine syndromes. MethodsBy comprehensively retrieving Chinese and international databases such as China National Knowledge Infrastructure， Wanfang， VIP Chinese Science and Technology Periodical Database （VIP）， and PubMed， all relevant literature on CGA animal models was collected. Based on the guidelines， the diagnostic criteria of both traditional Chinese and western medicine were summarized and organized. The evaluation indicators for the CGA model were constructed with reference to existing evaluation modes， and the CGA animal models were analyzed to systematically evaluate the clinical concordance of existing models. ResultsThe current methods used to construct CGA animal models mainly include monosodium urate crystal induction， high-protein diet induction （poultry lack urate oxidase）， and high-fat diet combined with urate oxidase inhibitors and joint injection. Based on 11 pieces of included literature， the traditional Chinese and western medicine scoring data of each model were extracted， and the average scoring values of all models were ultimately calculated. The results show that the average clinical concordances of existing CGA animal models in both traditional Chinese and western medicine are 43.33% and 64.44%， respectively. Among them， the model with the highest clinical concordance rate is the one with a high-fat diet combined with potassium oxonate to induce hyperuricemia plus joint injection， achieving 83.33% clinical concordance in western medicine and 60% in traditional Chinese medicine. This model aligns well with the pathogenic characteristics and pathological changes of clinical CGA. ConclusionAlthough current CGA animal models can simulate some pathological characteristics of CGA， they struggle to comprehensively reflect the complex pathological processes of CGA and the characteristics of traditional Chinese medicine syndromes. Therefore， in the future， it is necessary to establish the CGA animal models that incorporate the clinical disease and syndrome characteristics of traditional Chinese and western medicine and formulate the uniform model evaluation criteria， providing more precise tools for CGA mechanism research and the development of traditional Chinese medicine.

ObjectiveTo evaluate the therapeutic effect of Huazhuo SanJie Chubi presciption （HSCD） on chronic gouty arthritis （CGA） rats with low-grade inflammation and to explore the underlying mechanism with a focus on macrophage polarization. MethodsThe 41 male 6-week-old SD rats were randomly allocated， using the random number table， to a normal group （n=8） and a model group （n =33）. CGA with low-grade inflammation was induced in the model group by daily gavage of potassium oxonate （250 mg·kg^-1·d^-1） and hypoxanthine （300 mg·kg^-1·d^-1）， combined with intra-articular injection of a monosodium urate （MSU） crystal suspension （50 μL， 25 g·L^-¹） into the left ankle twice weekly. After 4 weeks of modeling， 3 rats were randomly selected from each group for model validation. The remaining successfully modeled rats were randomly divided into a model group， an HSCD group （10.35 g·kg^-1·d^-1， gavage once daily）， an M1 polarization agonist group （L-methionine sulfoximine， 300 mg·kg^-1， subcutaneous injection every other day）， an M1 polarization agonist + HSCD group， an M2 polarization inhibitor group （PD0325901， 10 mg·kg^-1·d^-1， gavage once daily）， and M2 polarization inhibitor + HSCD group. The corresponding drug or drug combination was administered according to group assignment， whereas rats in the normal and model groups received 0.5% carboxymethyl cellulose sodium （CMC-Na） vehicle （10.35 g·kg^-1·d^-1， gavage once daily）. All interventions were continued for four weeks. During the intervention period， except for the normal group， potassium oxonate （250 mg·kg⁻¹） and hypoxanthine （300 mg·kg^-1） were co-administered by gavage every other day to maintain the model. At the end of treatment， serum uric acid （SUA）， ankle joint diameter and joint swelling index were measured. The levels of high-sensitivity C-reactive protein （hs-CRP）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， chemokine C-C motif ligand 2 （CCL2）， S100 calcium-binding protein A8/A9 （S100A8/A9）， interleukin-10 （IL-10） and arginase-1 （Arg-1） in serum and joint fluid were determined by enzyme-linked immunosorbent assay （ELISA）. High-frequency ultrasound was used to assess MSU deposition in the ankle joint. Hematoxylin-eosin （HE） staining was performed to evaluate synovial histopathological changes. Quantitative Real-time PCR and immunofluorescence were used to detect the mRNA and protein expression of the M1 macrophage polarization markers inducible nitric oxide synthase （iNOS） and the M2 macrophage polarization marker scavenger receptor cysteine-rich type 1 protein M130 （CD163） in synovial tissue. ResultsCompared with the normal group， the model group showed significantly elevated SUA level and joint swelling index， and increased levels of pro-inflammatory cytokines， CCL2， and S100A8/A9 in both serum and joint fluid （P<0.05）， accompanied by MSU deposition and synovial inflammation in the ankle joint. The mRNA and protein expression levels of macrophage polarization M1/M2 markers iNOS and CD163 in synovial tissues were also significantly up-regulated （P<0.05）. Compared with model group， rats in HSCD group had significantly lower SUA levels， attenuated joint swelling， reduced serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in both serum and joint fluid， accompanied with alleviated MSU deposition and synovial inflammation （P<0.05）. HSCD markedly downregulated the mRNA and protein expression of M1 marker iNOS （P<0.05）， whereas it had no significant effect on the expression of M2 marker CD163. Compared with the M1 polarization agonist group， the M1 polarization agonist + HSCD group showed significantly reduced joint swelling， lower serum levels of pro-inflammatory cytokines， and decreased levels of CCL2 and S100A8/A9 in joint fluid （P<0.05）. In addition， synovial inflammatory cell infiltration and angiogenesis were attenuated， and iNOS mRNA and protein expression levels were significantly reduced （P<0.05）. Compared with the M2 polarization inhibitor group， the M2 polarization inhibitor + HSCD group exhibited reduced joint swelling， decreased levels of CCL2 and S100A8/A9 in joint fluid and ameliorated synovial inflammation （P<0.05）， whereas the levels of anti-inflammatory mediators （IL-10， Arg-1） and CD163 mRNA and protein expression were not significantly increased. ConclusionHSCD alleviates low-grade inflammation in CGA rats， at least in part， by inhibiting macrophage polarization toward the M1 phenotype.

ObjectiveThis paper aims to observe the effect of Huazhuo Sanjie Chubi prescription （HSCD） on the gouty bone erosion model rats and investigate its action mechanism. MethodsThirty-six two-month-old male SD rats were randomly divided into the blank group with nine rats and the modeling group with 27 rats. The rats in the modeling group were administered hypoxanthine solution at 300 mg·kg^-1·d^-1 and potassium oxonate solution at 250 mg·kg^-1·d^-1， combined with intra-articular injection of 200 μL monosodium urate （MSU） crystal suspension at 25 g·L^-1 into the right ankle joint （joint injection once every three days）， so as to induce the gouty bone erosion model. After four weeks of modeling， three rats were selected from these two groups to validate the model. The modeled 24 rats were randomly divided into the model group， HSCD group （10.35 g·kg^-1·d^-1）， allopurinol group （20 mg·kg^-1·d^-1）， and inhibitor group （LY294002， 10 mg·kg^-1·d^-1）， with six rats per group. Except for the blank group， rats in all other groups continued to receive hypoxanthine solution at 300 mg·kg^-1 and potassium oxonate solution at 250 mg·kg^-1 via gavage concurrently with administration to maintain modeling intervention. The rats in the HSCD group and allopurinol group received administration by gavage at the above doses. The rats in the inhibitor group received an intraperitoneal injection at the above dose. The rats in the blank group and model group received saline （10.35 g·kg^-1·d^-1） by gavage for four consecutive weeks. After administration， ankle joint swelling of the rats in all groups was observed， and the diameters were measured. Bone volume fraction （BV/TV） and bone surface area to bone volume （BS/BV） were observed and quantitatively analyzed by Micro-CT. Histopathological changes in the ankle joint were observed by hematoxylin-eosin （HE） staining and safranin O-fast green staining. The uric acid in the rats' serum was determined by enzyme colorimetry. The levels of inflammatory factors， including tumor necrosis factor-α （TNF-α）， interleukin （IL）-1β， and IL-6 were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of receptor activator of nuclear factor-κB ligand （RANKL） and phosphorylated （p）-phosphatidylinositol-3-kinase （PI3K） in ankle joint tissues of rats were detected by immunofluorescence staining. The mRNA levels of the proteins related to the bone erosion， including RANKL， tartrate-resistant acid phosphatase （TRAP）， cathepsin K （CTSK）， and matrix metalloproteinase-9 （MMP-9） in the ankle joint tissues of rats were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expressions of the proteins related to the bone erosion， including RANKL， CTSK， TRAP， MMP-9， and the proteins related to the PI3K/protein kinase B （Akt） signaling pathway， including PI3K， Akt， mammalian target of rapamycin （mTOR）， p-PI3K， phosphorylated protein kinase B （p-Akt）， and phosphorylated mammalian target of rapamycin （p-mTOR）， were detected by Western blot. ResultsCompared with the blank group， the modeling group showed marked ankle swelling and increased diameter. Micro-CT revealed an uneven articular surface and honeycomb-like bone erosion in the ankle joint. Quantitative analysis showed decreased BV/TV and increased BS/BV （P<0.05）. HE staining revealed a narrowed joint space， rough and discontinuous cartilage surfaces， reduced and unevenly distributed chondrocytes， partial hypertrophy， and blurred tidemarks， confirming successful model establishment. After four weeks of intervention， compared with those in the blank group， the rats in the model group exhibited severe ankle swelling and increased diameters （P<0.05）. Micro‑CT showed that the ankle joint surface was irregular， and bone erosion exhibited a honeycomb‑like morphology. The microstructural parameters of the bone revealed a decreased BV/TV and an increased BS/BV （P<0.05）. Histopathological examination revealed a narrowed joint space and severe articular cartilage destruction. The levels of uric acid in the serum and inflammatory factors （IL-1β， IL-6， and TNF-α） were increased （P<0.05）. The mRNA and protein levels of the proteins related to bone erosion in joint tissue， including RANKL， CTSK， TRAP， and MMP-9， were upregulated （P<0.05）. The ratios of p-PI3K/PI3K， p-Akt/Akt， and p-mTOR/mTOR in the proteins related to the PI3K/Akt signaling pathway were increased （P<0.05）. RANKL and p-PI3K protein fluorescence intensities were elevated （P<0.05）. Compared with those in the model group， the above indicators in all other administration groups showed varying degrees of improvement. The HSCD group and inhibitor groups exhibited more significant effects in reducing ankle swelling， improving bone erosion， bone microstructure （significant decrease in BV/TV and increase in BS/BV）， and the pathology of cartilage erosion， lowering inflammatory factor levels， downregulating the proteins related to the bone erosion， and suppressing activation of the PI3K/Akt/mTOR pathway （P<0.05）. The uric acid levels in rats' serum were reduced in both HSCD and allopurinol groups （P<0.05）. Compared with those in the HSCD group， the rats in the allopurinol group had larger ankle diameters （P<0.05）， more severe bone erosion and bone microstructure damage （P<0.05）， worse improvement of the pathology of cartilage erosion， higher levels of IL-6 and TNF-α （P<0.05）， elevated expressions of the proteins related to the bone erosion， higher expression ratio of proteins related to the PI3K/Akt signaling pathway （P<0.05）， and higher fluorescence intensities of RANKL and p-PI3K proteins （P<0.05）. The inhibitor group achieved comparable results to the HSCD group in improvements of bone microstructure and the reduction of IL-1β and IL-6， stronger suppression of TNF-α and PI3K/Akt/mTOR signaling pathway activation （P<0.05）， but weaker effects on cartilage repair and serum uric acid reduction （P<0.05）. ConclusionHSCD effectively reduces uric acid levels in serum， suppresses inflammatory factor secretion， and downregulates the expressions of proteins related to bone erosion， including RANKL， CTSK， TRAP， and MMP-9 in the joint tissues. Its action mechanism of improving gouty bone erosion may be associated with inhibition of the PI3K/Akt signaling pathway.

ObjectiveTo investigate the mechanism by which Wumeiwan suppresses the development and progression of colorectal cancer（CRC） through the regulation of fatty acid metabolic reprogramming， thereby providing new experimental evidence for the prevention and treatment of CRC. MethodsA total of 120 C57BL/6 mice were randomly divided into the blank group， model group， Wumeiwan high-， medium-， and low-dose groups（54， 27， 13.5 g·kg^-1）， and the mesalazine group（0.01 g·kg^-1）， with 20 mice in each group. Except for the blank group， all mice were subjected to azoxymethane（AOM）/dextran sulfate sodium（DSS） treatment to establish an inflammation-associated CRC model. One week after AOM injection， mice in the treatment groups received intragastric administration of the designated drugs， while the blank and model groups received an equal volume of purified water， continuing until 20 d after the intervention endpoint. Hematoxylin-eosin（HE） staining was used to observe colonic histopathological alterations， and immunohistochemistry for vascular endothelial growth factor（VEGF） was performed to evaluate neovascularization and tumor invasion. Metabolomics combined with Kyoto Encyclopedia of Genes and Genomes（KEGG） and metabolite set enrichment analysis（MSEA） was applied to identify key CRC-related metabolic pathways， which were further validated by transcriptomic Gene Ontology（GO） enrichment and gene heatmap analysis. Subsequently， Western blot was performed to determine the expression levels of core proteins in these pathways， and immunofluorescence was used to analyze their localization and co-expression patterns in tissues， thereby elucidating the mechanism of Wumeiwan from multiple biological dimensions. ResultsCompared with the blank group， mice in the model group exhibited a significant decrease in body weight and a significant increase in the disease activity index（DAI） score（P<0.05）， with pronounced colonic mucosal damage accompanied by aggravated tumor invasion. Compared with the model group， Wumeiwan intervention markedly improved body weight loss and reduced DAI score， attenuated mucosal injury， and significantly decreased VEGF expression level（P<0.05）. Multi-omics analysis revealed that differential metabolites and genes across groups were commonly enriched in fatty acid metabolism， fatty acid biosynthesis， and other lipid-related pathways. Relative to the blank group， the model group showed significant upregulation levels of fatty acid synthesis-related genes， including sterol regulatory element-binding protein 1（SREBP1）， fatty acid synthase（FASN）， stearoyl-CoA desaturase 1（SCD1）， as well as saturated fatty acids（P<0.05）. Compared with the model group， treatment with Wumeiwan significantly reduced the expression of key genes involved in fatty acid metabolic pathways， including SREBP1， FASN， and SCD1（P<0.05）. Western blot results further confirmed that proteins in this pathway were significantly elevated in the model group， whereas they were markedly downregulated following Wumeiwan treatment（P<0.05）. Immunofluorescence analysis demonstrated enhanced co-localization of SREBP1 with the cancer-associated fibroblast（CAF） marker α-smooth muscle actin（SMA） in the model group， whereas this co-localization signal was attenuated after Wumeiwan intervention（P<0.05）. ConclusionWumeiwan can improve survival outcomes and alleviate colonic pathological damage in CRC mice， its therapeutic mechanism may be closely associated with the regulation of fatty acid metabolic reprogramming mediated by the SREBP1/FASN/SCD1 signaling pathway.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Objective To investigate the epidemiological characteristics of malaria and provide a basis for developing improved prevention and control measures. Methods Data were obtained from the Chinese Disease Prevention and Control Information System. Malaria surveillance data for Nanning City from January 1,2023, to December 31,2024, were exported from the Infectious Disease Reporting Information Management Subsystem. The characteristics of the two groups of malaria cases were compared. Results A total of 103 imported malaria cases were reported in Nanning City in 2024, representing a 38.32% decrease compared with the same period of the previous year. No statistically significant difference were observed between cases reported in 2023 and 2024 in terms of average age, gender ratio, proportion of parasite species, and monthly reporting distribution;however, statistically significant differences were found in the proportion of reporting areas and current residence areas(χ2= 13.572 and 10.355, respectively; P = 0.001 and 0.035, respectively). The proportion of cases reported in Shanglin County and the proportion of cases residing in Shanglin County were both lower than those during the same period of the previous year. Conclusions The high aggregation of imported malaria cases in Nanning City has decreased. Medical institutions in areas other than Shanglin County should strengthen their vigilance against malaria.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective To study the application of autologous natural killer(NK)cells in the treatment of advanced renal cell carcinoma and the changes of immune function and tumor markers in patients.Methods 61 patients with advanced renal cell carcinoma admitted to Gansu Wuwei Tumour Hospital from March 2023 to April 2024 were divided into targeting group(31 cases,given supportive treatment combined with sunitinib malate capsules)and cell group(30 cases,autologous NK cells combined with targeting group)according to the patient's willingness to treat combined with propensity score matching.6 weeks was a treatment cycle,and all patients were treated for 4 cycles.The clinical efficacy of the two groups after 4 cycles of treatment and the occurrence of adverse reactions during treatment were statistically analyzed.The levels of serum cytokines,tumor markers,lymphocyte function and immune function were compared between the two groups before and after 4 cycles of treatment.Results After 4 cycles of treatment,the objective remission rate and disease control rate in the cell group were higher than those in the targeting group(P<0.05).After 4 cycles of treatment,the levels of serum hypoxia-inducible factor-1α(HIF-1α),vascular endothelial growth factor(VEGF),platelet-derived growth factor(PDGF),carcinoembryonic antigen,carbohydrate antigen 125,carbohydrate antigen 199 and alpha-fetoprotein in the two groups were lower than those before treatment,and those in the cell group were lower than those in the targeting group(P<0.012 5).After 4 cycles of treatment,the levels of serum interleukin-2,interleukin-6,tumor necrosis factor-β,interferon-γ,peripheral blood CD3+,CD4+,NK cells and CD4+/CD8+in the two groups were higher than those before treatment.The levels of serum interleukin-2,tumor necrosis factor-β,interferon-γ,peripheral blood CD3+and NK cells in the cell group were higher than those in the targeting group(P<0.012 5).The level of CD8+in peripheral blood was lower than that before treatment(P<0.012 5),but there was no significant difference between the two groups(P>0.012 5).During the treatment,there was no significant difference in the incidence of diarrhea,nausea and vomiting,alopecia,liver function damage,decreased platelet level and decreased neutrophil level between the cell group and the targeting group(P>0.05).Conclusion The treatment of advanced renal cell carcinoma with autologous NK cells could improve the level of serum cytokines,reduce the level of tumor markers,regulate the function of lymphocytes and immune function,and had a good therapeutic effect.At the same time,it would not increase the incidence of adverse reactions,and the safety was good.