In order to promote the innovative application of Sanjiao theory and Yingwei theory， this paper tries to apply the ''Sanjiao-Yingwei'' Qi transformation theory to the treatment of tumor diseases， integrating it with T cell exhaustion mechanism to elaborate on its scientific connotation and using network pharmacology and bioinformatics to elucidate the correlation between the anti-tumor mechanism of ''Sanjiao-Yingwei'' Qi transformation and T cell exhaustion. The ''Sanjiao-Yingwei'' Qi transformation function is closely related to the immunometabolic ability of the human body， and the ''Sanjiao-Yingwei'' Qi transformation system constitutes the immunometabolic exchange system within and outside the cellular environment. Cancer toxicity is generated by the fuzzy Sanjiao Qi， and the long-term fuzzy Sanjiao Qi is the primary factor leading to T cell exhaustion， which is related to the long-term activation of T cell receptors by the high tumor antigen load in the tumor microenvironment. Qi transformation malfunction of the Sanjiao produces phlegm and collects stasis， which contributes to T cell exhaustion and is correlated with nutrient deprivation， lipid accumulation， and high lactate levels in the immunosuppressed tumor microenvironment， as well as with the release of transforming growth factor-β and upregulated expression of programmed death receptor-1 by tumor-associated fibroblasts and platelets in the tumor microenvironment. Ying and Wei damage due to Sanjiao Qi transformation malfunction is similar to the abnormal manifestations such as progressive loss of exhausted T cell effector function and disturbance of cellular energy metabolism. Guizhi decoction， Shengming decoction， and Wendan decoction can correct T cell exhaustion and exert anti-tumor effects through multi-target and multi-pathways by regulating ''Sanjiao-Yingwei'' Qi transformation， and hypoxia inducible factor-1α （HIF-1α） may be one of the main pathways to correct T cell exhaustion. It was found that HIF-1α may be one of the important prognostic indicators in common tumors by bioinformatics. The use of the ''Sanjiao-Yingwei'' Qi transformation method may play an important part in improving the prognosis of tumor patients in clinical practice.

ObjectiveTo explore the effect and possible molecular mechanism of Qinghua Yichang Formula （清化益肠方， QYF） in treating acute radiation-induced intestinal injury mice via NOD-like receptor thermal protein domain associated protein 3 （NLRP3）. MethodsSixty C57BL/6J mice were randomly divided into control group， model group， pre-modeling medication group， post-modeling medication group， inhibitor group， and QYF plus inhibitor group， with 10 mice in each group.Except for the control group， the other five groups were irradiated with a single full dose to establish the acute radiation-induced intestinal injury mice model. The pre-modeling medication group and the QYF plus inhibitor group were continuously given 4 g/ml of QYF decoction by gavage before modeling， 0.2 ml each time， once a day for 7 days. The post-modeling medication group， pre-modeling medication group and QYF plus inhibitor group were given 4 g/ml of QYF decoction for 14 days after modeling. The control group， model group and inhibitor group were given 0.2 ml of normal saline once a day for 14 consecutive days. Two hours after irradiation， the inhibitor group and the QYF plus inhibitor group were given an intraperitoneal injection of 0.2 ml of the NLRP3 inhibitor MCC950 （concentration： 10 mg/kg）， once every two days. To observe the pathological changes in intestinal tissues， hematoxylin-eosin （HE） staining was used. Western blotting and RT-qPCR were used to detect the protein and mRNA expression levels of NLRP3 in intestinal tissues. Immunohistochemistry was used to detect the expression level of NLRP3， Caspase-1 and GSDMD in intestinal tissues. The proportion of CD4⁺ and CD8⁺ T cells in the spleens of mice were detected by flow cytometry. ELISA was used to determine the levels of IFN-γ， IL-18， and IL-1β in mice serum. ResultsHE staining showed no lesions in the intestinal tissue of mice in the control group. The mice in the model group had shortened intestinal villi， thinned mucosal layers， multifocal mucosal necrosis in the lamina propria， and local neutrophil infiltration. The pathological damage of intestinal tissue of mice in each medication group was improved to varied degrees， among which the QYF plus inhibitor group showed most obvious improvement. Compared to those in the control group， the protein and mRNA expression levels of NLRP3 in the intestinal tissue of mice in the model group significantly increased， with higher NLRP3， Caspase-1， and GSDMD protein expression in the intestinal tissue， increased proportion of CD4⁺ T cells in spleen， decreased proportion of CD8⁺ T cells， and increased levels of IFN-γ， IL-18 and IL-1β in serum （P＜0.05）. Compared to those in the model group， the above indicators in the other medication groups were all improved （P＜0.05）.The NLRP3， Caspase-1， and GSDMD proteins in the pre-modeling medication group were lower than those in the post-modeling medication group （P＜0.05）； and the NLRP3 mRNA level in the QYF plus inhibitor group was lower than that in the inhibitor group （P＜0.05）. ConclusionQYF may play a role in preventing and treating acute radiation-induced intestinal injury by inhibiting the expression of NLRP3.

Objective To evaluate the efficacy of medroxyprogesterone acetate(MA)plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia(AEH)and early-stage grade 1 endometrial adenocarcinoma(G1 EAC)and the recurrence rate after treatment.Methods Sixty patients(aged 20-42 years)with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups(n=30)to receive oral MA treatment at the daily dose of 160 mg(control)or MA plus oral metformin(850 mg,twice a day)for at least 6 months.The treatment could extend to 12 months until a complete response(CR)was achieved,and follow-up hysteroscopy and curettage were performed every 3 months.For all the patients who achieved CR,endometrial expressions of IGFBP-rP1,p-Akt and p-AMPK were detected immunohistochemically.Results A total of 58 patients completed the treatment.After 9 months of treatment,23(76.7%)patients in the combined treatment group and 20(71.4%)in the control group achieved CR;two patients in the control group achieved CR after converting to the combined treatment.The recurrence rate did not differ significantly between the control group and combined treatment group(30.0%vs 22.7%,P>0.05).Ten(35.7%)patients in the control group experienced significant weight gain of 5.7±6.1 kg,while none of the patients receiving the combined treatment exhibited significant body weight changes.Compared with the control group,the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.Conclusion Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC,and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.

Adjuvant chemoradiotherapy,molecular targeted therapy,and immunotherapy are frequently employed to extend the survival of patients with advanced gastric cancer(GC).However,most of these treatments have toxic side effects,drug resistance,and limited improvements in survival and quality of life.Therefore,it is crucial to discover and develop new medications targeting GC that are highly effective and have minimal toxicity.In previous studies,the total terpene extract from the stem of Celastrus orbiculatus demonstrated anti-GC activity;however,the specific mechanism was unclear.Our research utilising co-immunoprecipitation-mass spectrometry(Co-IP-MS),polypyrimidine tract binding protein 1(ptbp1)clustered regularly interspaced short palindromic repeat-associated protein 9(Cas9)-knockout(KO)mouse model,tissue microarray,and functional experiments suggests that alpha actinin-4(ACTN4)could be a significant biomarker of GC.PTBP1 influences actin cytoskeleton restructuring in GC cells by interacting with ACTN4.Celastrus orbiculatus stem extract(COE)may directly target ACTN4 and affect the interaction between PTBP1 and ACTN4,thereby exerting anti-GC effects.

Objective To evaluate the efficacy of medroxyprogesterone acetate(MA)plus metformin as the primary fertility-sparing treatment for atypical endometrial hyperplasia(AEH)and early-stage grade 1 endometrial adenocarcinoma(G1 EAC)and the recurrence rate after treatment.Methods Sixty patients(aged 20-42 years)with AEH and/or grade 1 EAC limited to the endometrium were enrolled prospectively and randomized into two groups(n=30)to receive oral MA treatment at the daily dose of 160 mg(control)or MA plus oral metformin(850 mg,twice a day)for at least 6 months.The treatment could extend to 12 months until a complete response(CR)was achieved,and follow-up hysteroscopy and curettage were performed every 3 months.For all the patients who achieved CR,endometrial expressions of IGFBP-rP1,p-Akt and p-AMPK were detected immunohistochemically.Results A total of 58 patients completed the treatment.After 9 months of treatment,23(76.7%)patients in the combined treatment group and 20(71.4%)in the control group achieved CR;two patients in the control group achieved CR after converting to the combined treatment.The recurrence rate did not differ significantly between the control group and combined treatment group(30.0%vs 22.7%,P>0.05).Ten(35.7%)patients in the control group experienced significant weight gain of 5.7±6.1 kg,while none of the patients receiving the combined treatment exhibited significant body weight changes.Compared with the control group,the patients receiving the combined treatment showed enhanced endometrial expressions of IGFBP-rP1 and p-AMPK with lowered p-Akt expression.Conclusion Metformin combined with MA may provide an effective option for fertility-sparing treatment of AEH and grade 1 stage IA EAC,and the clinical benefits of metformin for controlling MA-induced weight gain and promoting endometrial expressions of IGFBP-rP1 and p-AMPK while inhibiting p-Akt expression warrants further study.

ObjectiveTo investigate the effect and mechanism of pachymic acid （PA） in Poria on the invasion and metastasis of renal carcinoma cells. MethodThe effect of PA （0， 20， 40， 80， 160 μmol·L^-1） on cell viability was detected by cell counting kit-8（CCK-8）， and the dose of PA was selected for subsequent experiments. The effect of PA （0， 20， 40， 80 μmol·L^-1） on cell proliferation was evaluated by colony formation assay. The effect of PA （0， 20， 40， 80 μmol·L^-1） on cell adhesion ability was observed by cell adhesion assay. The effect of PA （0， 20， 40， and 80 μmol·L^-1） on cell invasion and metastasis was investigated by Wound healing assay and Transwell invasion assay. The inhibitory effect of PA （0， 20， 40， 80 μmol·L^-1） on cell motility was further observed and verified by high-content imaging technology. The effects of PA （0， 20， 40， 80 μmol·L^-1） on the expression of matrix metalloproteinase （MMP）/tissue inhibitor of metalloproteinasas （TIMP） related to invasion and metastasis and Smads were detected by Western blot. ResultCCK-8 results showed that compared with the blank group， the PA groups showed decreased cell viability（P<0.01）， with the half-maximal inhibitory concentration （IC₅₀） of ACHN cells of 70.42 μmol·L^-1 at 24 h. Colony formation assay showed that the number of cell clonal groups in the PA groups was reduced compared with that in the blank group（P<0.01）. Cell adhesion assay showed that compared with the blank group， the PA groups displayed reduced cell adhesion（P<0.01）. Wound healing assay showed that the wound healing rate of cells in the PA groups was lower than that in the blank group （P<0.05，P<0.01）. Transwell invasion assay showed that compared with the blank group， the number of transmembrane cells in PA groups was reduced（P<0.01）. High-content imaging showed that the cumulative migration distance of cells in the PA groups was shorter than that in the blank group（P<0.01）. The results of Western blot showed that the protein expression of MMP-2 and MMP-9 in the PA groups decreased （P<0.01）， and TIMP-1 protein expression increased （P<0.01） compared with those in the blank group. In addition， compared with the blank group， the PA groups showed decreased protein expression of Smad2 and Smad3 （P<0.01）. ConclusionPA can inhibit the invasion and metastasis of renal carcinoma cells presumably through regulating the homeostasis of MMP/TIMP by Smad2/3.

Background/Aims: Chemoresistance is a common event after cancer chemotherapy, which is associated with the deregulation of circular RNAs (circRNAs). The objective of this study was to clarify the role of circ-LDLRAD3 in cisplatin (DDP)-resistant gastric cancer (GC). Methods: The expression of circ-LDLRAD3, miR-588, and SRY-box transcription factor 5 (SOX5) mRNA was detected by quantitative real-time polymerase chain reaction. Cell viability and the half maximal inhibitory concentration (IC 50 ) value were measured by CCK8 assay. Cell proliferation was assessed by colony formation and EdU assays. Cell apoptosis and cell invasion were assessed by flow cytometry assay and transwell assay, respectively. The expression of SOX5 protein was detected by Western blotting. A xenograft model was established to verify the role of circ-LDLRAD3 in vivo. Exosomes were isolated by differential centrifugation and identified by transmission electron microscopy and the expression of exosome-related proteins. Results: circ-LDLRAD3 was overexpressed in DDP-resistant GC tissues and cells. circ-LDL-RAD3 knockdown decreased the IC 50 of DDP-resistant cells and suppressed cell proliferation, survival and invasion. miR-588 was a target of circ-LDLRAD3, and miR-588 inhibition attenuated the inhibition of DDP resistance, proliferation, survival and invasion in DDP-resistant GC cells caused by circ-LDLRAD3 knockdown. SOX5 was a target of miR-588, and the inhibition of the DDP resistance, proliferation, survival and invasion of DDP-resistant GC cells by miR-588 restoration was largely rescued SOX5 overexpression. circ-LDLRAD3 knockdown inhibited DDP resistance and tumor growth in vivo. circ-LDLRAD3 was overexpressed in exosomes isolated from DDP-resistant GC cells. Conclusions circ-LDLRAD3 knockdown reduced DDP resistance and blocked the malignant development of DDP-resistant GC by modulating the miR-588/SOX5 pathway.

Objective:To investigate the nutrition researches in radiation oncology, identify the hot topics, and inform the future development of radiotherapy nutrition.Method:Web of Science Core Collection was searched and Citespace-based analysis was performed for the bibliometric analysis of research papers on tumor radiotherapy nutrition.Results:A total of 1 243 articles were included, and there was an increasing trend in the annual number of articles published from 2014 to 2021. The top three countries with the most publications were the United States, China and Australia. In addition to radiotherapy, tumor and nutrition, common keywords in these articles included quality of life, weight loss, head and neck cancer, parenteral nutrition, enteral nutrition, and dietary intake.Conclusions:Domestic and foreign scholars have paid more and more attention to tumor radiotherapy nutrition. In recent years, the research hot topics are mainly head and neck tumors, nutritional support methods, concurrent chemoradiotherapy and patient prognosis. There was a scarcity of collaborations between domestic and foreign institutions. Institutions such as the State Key Laboratory in Oncology in South China, Sun Yat-sen University and Peking University have been continuously advancing the development of radiotherapy nutrition and have carried out a lot of researches. The gap between China and abroad is narrowing. Researches in China needs to be improved in terms of the depth and breadth. In the future, nutrition researches can further explore the aspects such as experimental protocol publication and the correlation of psychology and nutrition, strengthen international collaboration, and enhance international impact with high-quality publications.

Objective:To explore the diagnostic value of virtual monoenergetic image (VMI) and electron density map (EDM) generated by non-contrast dual-layer spectral detector CT in acute pulmonary embolism(APE).Methods:The clinical and imaging data of 27 patients (41 lesions) who underwent CT pulmonary angiography (CTPA) using dual-layer spectral detector CT and were diagnosed with APE in the Third Affiliated Hospital of Sun Yat-sen University from October 2022 to May 2023 were retrospectively analyzed. All patients received a dual-layer spectral detector CT non-contrast scan. Based on the non-contrast scan data, conventional 120 kVp polyenergetic images (PI), virtual monoenergetic images (40, 70, 100 keV VMI), electron density maps (EDM), and effective atomic number maps (Z eff) were respectively reconstructed. Taking CTPA as the gold standard, the detection rate of APE in different reconstruction images of non-contrast scan were evaluated. The vascular lesion was used as the pulmonary embolism group and the corresponding position of the normal vessel at the same level of the diseased vessel as the control group, and the Wilcoxon rank-sum test was used to compare the differences of CT values on PI and 40, 70, and 100 keV VMI (CT PI, CT 40 keV, CT 70 keV, CT 100 keV) as well as the ED values on the EDM, and the Z eff value on the Z eff images between the 2 groups. Parameters with statistically significant differences were included in a multifactor logistic regression, resulting in the construction of a logistic regression model. Receiver operator characteristic curve and area under curve (AUC) were applied to evaluate the diagnostic efficiency of different spectral quantitative parameters and logistic regression model in identifying pulmonary embolism group from normal control group. Results:The detection rates of APE on PI, EDM, Z eff map, and EDM and Z eff map fusion images were 14.6% (6/41), 82.9% (34/41), 51.2% (21/41), and 97.6% (40/41), respectively. CT PI, ED, CT 40 keV, CT 70 keV and CT 100 keV in pulmonary embolism group were statistically higher than those in control group ( Z values were 1 009.00, 1 024.50, 1 038.00, 1 079.00 and 1 076.00, respectively, P<0.05). Finally, CT PI, CT 40 keV, and CT 100 keV were selected to construct the logistic regression model. The AUC, sensitivity, specificity, and accuracy of the logistic regression model for distinguishing the embolism group from the control group were 0.771, 0.769, 0.744, and 0.756, respectively. Conclusion:Non-contrast images of dual-layer spectral detector CT VMI and EDM have some clinical value in detecting and diagnosing APE.

Objective: To investigate the value of combined stool syndecan-2 (SDC2) and tissue factor pathway inhibitor 2 ( TFPI2) gene methylation testing in the early screening of colorectal cancer． Methods : 106 patients with colorectal cancer (colorectal cancer group) ，75 patients with advanced adenoma ( advanced adenoma group) and 35 patients with non-advanced adenoma (non-advanced adenoma group) were selected as study subjects，and 153 patients with other gastrointestinal disorders and 182 patients with negative colonoscopy results during the same period were selected as the control group．The quantitative methylation-specific PCR(qMSP) method was used to detect SDC2 and TFPI2 gene methylation in the stool specimens of all subjects．The sensitivity and specificity of the combined SDC2 and TFPI2 gene methylation assay for the detection of colorectal cancer and adenoma were evaluated using colonoscopy and pathology results as the gold standard. Results : Among 106 patients with colorectal cancer， the sensitivity of combined methylation test was 93. 4% ; among 75 patients with advanced adenoma，the sensitivity of combined methylation test was 62. 7% ; among 35 patients with non-advanced adenoma，the sensitivity of combined methylation test was 34. 3% ; the specificity of the combined SDC2 and TFPI2 gene methylation test for colorectal cancer and adenoma screening was 94. 6%． Conclusion The combined SDC2 and TFPI2 gene methylation test has high sensitivity for colorectal cancer and its early lesions，and it also maintains high specificity.