This article systematically explores the traditional Chinese medicine （TCM） pathogenesis evolution and metastatic mechanisms of advanced gastric cancer from the perspective of "phlegm-toxin flowing infusion". Based on this theory， it is proposed that advanced gastric cancer presents a pathogenesis evolution characterized by healthy qi depletion， phlegm-toxin flowing infusion， and collateral damage with blood stasis. Healthy qi depletion is the root of the disease， in which spleen and kidney insufficiency leads to weakened healthy qi and inability to resist pathogenic factors. Phlegm-toxin flowing infusion is the core pathogenesis， where phlegm-dampness and cancer toxin intertwine and migrate to other organs along with qi movement. Collateral damage with blood stasis constitutes the final pathological stage of metastasis， where phlegm-toxin obstruction damages the collaterals， and congealed qi and blood form accumulations. On this basis， the meridian pathways and metastasis mechanisms of advanced gastric cancer spreading to multiple sites such as the liver， peritoneum， lungs， bones， brain， ovary， and lymph nodes are further analyzed， providing references for clinical management and research of this disease.

ObjectiveTo investigate the association between the maintenance treatment of modified Yiqi Huoxue Jiedu Formula （益气活血解毒方） or poly ADP ribose polymerase （PARP） inhibitors and the recurrence and metastasis of advanced ovarian cancer. MethodsA case-control study design was employed， dividing patients with advanced ovarian cancer into two groups based on the occurrence of recurrence and metastasis following first-line maintenance treatment. Patients with recurrence and metastasis comprised the case group， while those without recurrence and metastasis served as the control group. The previous first-line maintenance treatment method was set as the exposure factor in the study （with the use of modified Yiqi Huoxue Jiedu Formula defined as exposed and PARP inhibitors defined as unexposed）. Basic information was collected for both groups， including the achievement of satisfactory R0 surgery， age， stage， neoadjuvant chemotherapy， lymph node metastasis， germline BRCA1/2 mutations， homologous recombination deficiency positivity， first-line maintenance treatment method （modified Yiqi Huoxue Jiedu Formula or PARP inhibitors）， and CA125 levels after the last chemotherapy. The baseline data of the two groups were assessed for differences. If there exists difference， a 1∶1 nearest neighbor matching method was used for propensity score matching. Univariate and multivariate logistic regression analyses were employed to evaluate the association between the modified Yiqi Huoxue Jiedu Formula or PARP inhibitors and the recurrence and metastasis of ovarian cancer. ResultsA total of 201 patients with advanced ovarian cancer were included， with 97 in the case group and 104 in the control group. Both groups showed statistically significant differences in R0 surgery， stage， neoadjuvant chemotherapy， and CA125 levels after the last chemotherapy （P＜0.05）， indicating baseline imbalance. After propensity score matching， there were 71 patients in both the case and control groups， achieving baseline balance （P＞0.05）. Univariate logistic regression analysis indicated that the achievement of satisfactory R0 surgery （P = 0.006）， disease stage （P = 0.001）， the use of neoadjuvant chemotherapy （P = 0.024）， treatment modality （P = 0.006）， and CA125 levels after the last chemotherapy （P = 0.013） were associated with the recurrence and metastasis of ovarian cancer. Multivariate logistic regression analysis revealed that disease stage was an independent influencing factor for the recurrence and metastasis of ovarian cancer （P = 0.030）， whereas the P-value for the correlation between first-line maintenance treatment and ovarian cancer was 0.188. ConclusionFirst-line maintenance treatment of ovarian cancer patients with the use of modified Yiqi Huoxue Jiedu Formula or PARP inhibitors does not correlate with the recurrence and metastasis of ovarian cancer.

ObjectiveTo analyze the distribution of traditional Chinese medicine （TCM） syndrome elements in patients with immune-related adverse events （irAEs） associated with malignant tumor immunotherapy and to explore the influencing factors for the occurrence of irAEs. MethodsClinical data were retrospectively collected from malignant tumor patients treated with programmed death-1 （PD-1） inhibitors， including demographic information， tumor history， duration of immunotherapy， occurrence of irAEs， types and grades of irAEs （G1-G5）， and TCM four-diagnostic information. Patients were divided into irAEs group and the non-irAEs group based on the occurrence of irAEs. Propensity score matching （PSM） at a 1∶2 ratio was performed to balance baseline characteristics between groups. Syndrome elements before treatment and cumulative contributions of syndrome elements before and after irAEs onset were evaluated using the "Syndrome Elements Differentiation Scale". Logistic regression analysis was conducted to identify factors associated with the occurrence of irAEs. The use of glucocorticoids in the irAEs group was also analyzed. ResultsAfter 1∶2 matching， 59 patients were included in the irAEs group and 118 were in the non-irAEs group. No statistically significant differences were found between groups in terms of age， gender， primary tumor site， pathological type， or tumor stage （P＞0.05）. Patients in the non-irAEs group were more likely to have received targeted therapy， while the irAEs group had a longer duration of immunotherapy and a higher rate of positive programmed death-ligand 1 （PD-L1） expression （P＜0.05）. In total， 72 irAEs events occurred among 59 patients， with an overall incidence rate of 19.4% （59/304） and a grade 3~5 incidence rate of 6.8% （4/59）， mainly presenting as cardiotoxicity， nephrotoxicity， and pneumotoxicity.Before immunotherapy， the top three syndrome elements in the irAEs group were spleen （71.2%， 42/59）， kidney （42.4%， 25/59）， and lung （39.0%， 23/59）. For the pathogenic nature elements， yin deficiency （52.5%， 31/59）， phlegm （40.7%， 24/59）， and dampness （35.6%， 21/59） ranked highest. Compared to the non-irAEs group， the distribution of spleen， kidney， liver， yin deficiency， and qi deficiency elements showed significant differences in the irAEs group （P＜0.05）. After the occurrence of irAEs， the cumulative contributions of spleen， lung， stomach， heart， yin deficiency， qi deficiency， and yang hyperactivity elements increased significantly （P＜0.05）. Multivariate Logistic regression analysis indicated that duration of immunotherapy， spleen syndrome element， kidney syndrome element， liver syndrome element， yin deficiency element， and qi deficiency element were independent risk factors for irAEs （P＜0.05 or P＜0.01）. Among the irAEs patients， 15 received glucocorticoid combined with TCM treatment， while 6 received glucocorticoid therapy alone. Patients receiving combined treatment required lower doses and shorter courses of glucocorticoids compared to those treated with glucocorticoids alone （P＜0.05）. ConclusionIn malignant tumor patients， spleen， kidney， lung， yin deficiency， phlegm， dampness， and qi deficiency are the predominant syndrome elements before and after the occurrence of irAEs. However， elements such as heat and qi stagnation significantly increase after irAEs onset. Duration of immunotherapy， spleen， kidney， liver syndrome elements， yin deficiency， and qi deficiency are independent risk factors for the development of irAEs.

Objective:To analyse the 3D-Flair MRI manifestations of the inner ear, vestibular function status, and their correlation with hearing treatment outcomes in patients with severe sudden sensorineural hearing loss (SSNHL), and to explore potential prognostic indicators for sudden deafness.Methods:The clinical data of adult patients with unilateral profound sudden sensorineural hearing loss were retrospectively analyzed in Otorhinolaryngology Department of Shandong Provincial ENT Hospital from March 2018 to August 2020. Patients were categorized based on the results of their inner ear 3D-Flair MRI into two groups: the normal MRI group and the abnormal MRI group. The abnormal group was further divided into three subgroups: those with non-absorbed high signal in the inner ear, those with absorbed high signal, and those with destruction of the blood-labyrinth barrier. SPSS 26.0 statistical software was applied to analyze the differences in hearing efficacy, caloric tests, vestibular evoked myogenic potentials (VEMP), video head impulse tests (vHIT), and the incidence of dizziness/vertigo among various patient groups.Results:A total of 191 patients with complete data were collected (97 males and 94 females, aged from 13 to 69 years old). There were 50 cases in the normal inner ear 3D-Flair MRI group. A total of 141 cases were found in the group with abnormal 3D-Flair MRI, including 50 cases of high signal unabsorbed, 71 cases of absorption high signal and 20 cases of blood labyrinth barrier destruction. There were no significant differences in age, sex, lateral ratio of hearing loss and course of disease among four groups (all P>0.05).The significant efficiencies of hearing recovery, in the group with normal 3D-FLAIR MRI were better than those in the abnormal group ( P<0.05) after treatment. Among the four groups, there were significant differences in the apparent efficiency and total effective rate between the normal group and the inner ear high signal absorption group ( χ2=4.007, P=0.045; χ2=6.925, P=0.009). The abnormal rates of bithermal caloric test, vHIT results and dizziness/vertigo symptoms in the abnormal group were higher than those in the normal group ( P<0.05). There were significant differences in oVEMP abnormality rate, vHIT abnormality rate and incidence of dizziness/vertigo among the three groups with 3D-FLAIR MRI abnormality ( P<0.05). There were significant differences in caloric test, oVEMP, vHIT abnormality rate and incidence of dizziness/vertigo among the four groups ( P<0.05). The positive rates of caloric test, cVEMP test and vHIT test in patients with dizziness/vertigo were higher than those in patients without dizziness/vertigo ( P<0.05). The abnormal rates of posterior semicircular canal and horizontal semicircular canal in patients with dizziness/vertigo were significantly increased ( P<0.05) than patients without dizziness/vertigo. The recovery rate, effective rate and total effective rate of patients without dizziness/vertigo were significantly better than those with dizziness/vertigo ( P<0.05). Conclusions:The 3D-Flair MRI of the inner ear and vestibular function tests have reference value for the prognosis assessment of patients with severe sudden sensorineural hearing loss. Abnormal 3D-FLAIR MRI of the inner ear, especially absorption high signal, is associated with high incidence of vestibular dysfunction and dizziness/vertigo, with poor prognosis. Patients with severe sudden sensorineural hearing loss who have symptoms of dizziness/vertigo are more likely to exhibit abnormal results in vestibular function tests, with a higher susceptibility to involvement of the posterior and horizontal semicircular canals.

Objective:To analyze the current status and trend of the mortality burden of cardiovascular disease in China from 2010 to 2021.Methods:Data related to cardiovascular disease mortality and disability-adjusted life year (DALY) were extracted from the Global Burden of Disease Study 2021 (GBD2021) database. The age-standardized mortality rate and DALY rate were calculated, using the 2021 world standard population estimated by GBD2021. Joinpoint 5.2.0 software was used to calculate the mortality rate, standardized mortality rate, DALY rate, standardized DALY rate, annual percent change (APC), average annual percent change (AAPC), and 95% CI of cardiovascular disease in China from 2010 to 2021. Results:The mortality rate of cardiovascular disease was 357.44/100 000, and the age-standardized mortality rate was 280.11/100 000 in China in 2021. The DALY rate was 7 043.33/100 000, and the age-standardized DALY rate was 5 120.06/100 000. From 2010 to 2021, the mortality rate and DALY rate of cardiovascular disease in China showed an upward trend (AAPC was 1.58% and 0.83%, respectively, both P<0.05), and the standardized mortality rate and standardized DALY rate showed a downward trend (AAPC was -2.13% and -2.02%, respectively, both P<0.05). The mortality burden of cardiovascular disease was higher in males (mortality rate 392.80/100 000, DALY rate 8 156.19/100 000) than in females (mortality rate 320.38/100 000, DALY rate 5 876.87/100 000). With the increase older in age, the mortality burden of cardiovascular disease in China decreased first and then increased. China ranked high in the mortality burden of cardiovascular disease among G20 member countries. Conclusions:The death burden of cardiovascular disease is serious in China. The mortality rate and DALY rate of cardiovascular disease in China showed an increasing trend from 2010 to 2021, and the standardized mortality rate and standardized DALY rate of cardiovascular disease ranked high in G20 member countries. The death burden of cardiovascular disease was more serious in men and the elderly. It is necessary to develop more comprehensive prevention, treatment, and rehabilitation measures for men and the elderly to reduce mortality and disability rates, decrease the disease burden, and improve the quality of life.

Objective:To analyze the conventional ultrasound（CUS）and contrast-enhanced ultrasound（CEUS）features of hepatic lymphoma，and to investigate the value of CEUS in the diagnosis of hepatic lymphoma.Methods:The images of 39 patients（39 lesions）with hepatic lymphoma pathologically confirmed by surgery and puncture from March 2012 to July 2024 at Zhongshan Hospital，Fudan University were retrospectively analyzed. Evaluations of CUS included the echogenicity，morphology，color Doppler flow imaging（CDFI）situation，evaluations of CEUS included enhancement type，enhancement degree compared to the peripheral normal liver parenchyma and time to enhancement.Results:In the 39 lesions，hypoechoic lesions were detected in 31（79.49%，31/39）patients on CUS. CDFI detected linear or branched color flow signals inside the lesions in 21（53.85%，21/39）lesions，and peripheral color flow signals around the lesions in 3 lesions，while arterial flow signals were detected in 16 of them，with a resistance index of 0.50～0.77（0.67 ± 0.02）. In addition，signs of non-compacted normal blood vessels passing through the lesions were detected in 5 lesions. After injection of contrast medium，39 lesions showed different degrees of enhancement，mainly showed entirety homogeneous enhancement，during the arterial phase of CEUS，34（87.18%，34/39）lesions showed fast enhancement，and when the enhancement reached the peak，26（66.67%，26/39）lesions revealed hyper-enhancement，showing “fast progression”. There were 38（97.44%，38/39）lesions in the portal and delayed phases showed “fast forward”.Conclusions:CUS and CEUS can provide some value in the diagnosis and differential diagnosis of hepatic lymphoma.

Objective:To investigate the value of targeted three-dimensional contrast-enhanced ultrasound（3D-tCEUS）in efficacy evaluation of non-surgical treatments for renal cell carcinoma（RCC）.Methods:Forty nude mice with subcutaneous xenograft tumor model of human RCC（786-O cells）were divided into four groups based on different treatment methods：control，thermal ablation（TA），sunitinib（Suni），and TA+Suni. 3D-tCEUS were performed on days 1，3，7，and 14 post-treatment using self-developed vascular endothelial growth factor receptor 2（VEGFR2）targeted microbubbles. Tumor overall volume（V T）and non-enhanced volume（V N）were measured，from which the volume of the active（enhanced）region was calculated as V A = V T - V N. The tumor total and active area volume was standardized as V T st and V A st（standardized tumor volume = tumor volume after treatment / tumor volume at the beginning of treatment）. Tumor growth curves were plotted and tumor inhibition rates calculated for V T and V A respectively. Quantitative parameters，including the area under the curve（AUC）and the difference in peak intensity before and after burst（dTE），were obtained from the viable tumor enhanced region，and the standardized targeted quantitative parameters were derived by calculating the ratios of parameters at various time points post-treatment to those pre-treatment. The differences in V T st，V A st，AUC and dTE between different treatment groups at different time points were compared. At the end of the experiment，tumor tissues were obtained for immunohistochemical staining to observe the expression of VEGFR2 and CD31 antigens. Results:During the treatment period，no statistically significant differences in weight changes were observed among groups（all P > 0.05）. When V T was taken as the research object，V T st increased across all groups during the treatment period，with the TA group showing the most significant growth，while the TA + Suni group exhibited the smoothest increase in growth curve. When analyzing the tumor enhanced region，tumor growth trend of V A st was different with V T st for all groups；the Suni group showed a slow upward trend，whereas the TA + Suni group showed a continuous decline. Significant differences in tumor inhibition rate originated from V T and V A were noted within the same experimental group（ P < 0.05 for all experimental groups）. One day post-treatment，the AUC and dTE of the TA group were higher than that of the Control group，while the dTE of the TA + Suni group was lower than that of the Control group（all P < 0.05）. By day 3，statistically significant differences in AUC and dTE were observed between each experimental group and Control groups（all P < 0.05）. At day 14，the TA group showed increased AUC and dTE compared with those before treatment，while all other groups，particularly Suni group and TA + Suni group，demonstrated significant reductions（all P < 0.05）. Immunohistochemical results revealed the highest VEGFR2 and CD31 positivity in the TA group，followed by the Control group，while the Suni and TA + Suni groups exhibited lower rates. Conclusions:The combination of TA and targeted therapy effectively induces RCC cells death，demonstrating superior efficacy compared to monotherapy. 3D-tCEUS serves as a accurate and reliable tool for early evaluating the efficacy of non-surgical RCC treatments.

Objective:To explore the differences between clinical-pathological-ultrasound features in hepatocellular carcinoma（HCC）with negative and positive des-gamma-carboxy prothrombin（DCP）.Methods:A retrospective analysis was conducted on 649 patients with pathologically confirmed HCC at Zhongshan Hospital，Fudan University from April 2020 to May 2024. Patients were stratified into DCP-negative（177 cases，<40 mAU/ml）and DCP-positive（472 cases，≥40 mAU/ml）groups. Clinical data，pathological features，and ultrasound findings were collected. Conventional ultrasound and contrast-enhanced ultrasound（CEUS）imaging characteristics were analyzed and compared between the two groups，and the correlation between ultrasound features and pathological characteristics were analyzed.Results:The DCP-negative group exhibited a lower incidence of microvascular invasion（10.17% vs. 34.75%， P<0.001）and smaller median tumor diameter（23 mm vs. 40 mm， P<0.001）. Heterogeneous internal echogenicity was less frequent in DCP-negative tumors［48.59%（86/177） vs. 74.58%（352/472）， P<0.001］. CEUS revealed higher rates of arterial-phase iso-enhancement（6.78% vs. 1.69%）and absence of washout（13.56% vs. 4.45%）in DCP-negative HCC（both P<0.001）. CEUS LI-RADS classification showed fewer LR-5 lesions［50.85%（90/177） vs. 59.53%（281/472）］in DCP-negative group（ P<0.001）. Conclusions:HCC with different DCP states has different clinical-pathological-ultrasound features. DCP-negative HCCs are more likely to show atypical enhancement patterns characteristic of HCC.

Objective To investigate the prognostic role of serum beta 2-microglobulin(β2M)as a systemic inflammatory biomarker in hospitalized patients with exacerbation of COPD,compared with other inflammatory biomarkers.Methods We retrospectively analyzed hospitalized patients with exacerbated COPD as the first diagnosis at Beijing Chao-Yang hospital,P.R.China,from December 31,2012 to December 28,2017.Serum β2M levels,laboratory and clinical indexes were measured or collected on admission,and all patients were followed up for 90 days.The prognostic performance of β2M was compared with the neutrophils-lymphocytes ratio(NLR),C-reactive protein values(CRP)and white blood cell(WBC)using MedCalc.Results For 30-day mortality,β2M,NLR,and CRP showed significant predictive value(all P<0.001)and were better than WBC(P=0.044,0.003 and 0.030,respectively)in hospitalized patients with exacerbated COPD,while WBC had no predictive significance.For 90-day mortality,β2M,NLR,CRP,and WBC were all statistically significant,but only NLR outperformed WBC(P=0.004).No significant differences were observed among β2M,NLR,and CRP.Conclusion As a systemic inflammatory biomarker,serum β2M was a useful prognostic biomarker for short-term death in hospitalized patients with COPD exacerbations.It performed slightly better than NLR and CRP for 30-day mortality prediction and slightly superior to CRP and slightly inferior to NLR for 90-day mortality prediction.

Objective To evaluate the evidence about impact of physical activity(PA)on glycemic control and related health out-comes in patients with type 2 diabetes mellitus(T2DM).Methods Adhering to PRISMA guideline,systematic reviews and meta-analyses published between 2017 and 2024 were retrieved from the databases such as Medline,Embase and Cochrane Library.Two researchers independently ex-tracted data and assessed the quality using AMSTAR2.The included systematic reviews were systematically re-viewed.Results Eight systematic reviews were included,with six rated as high quality and two as low quality.Various forms of PA interventions,such as aerobic exercise,resistance training,combined training and high-intensity interval train-ing,might significantly reduce glycated hemoglobin,enhance cardiorespiratory fitness,lower cardiovascular risk factors(such as body mass,blood pressure and blood lipids),and decrease the risk of diabetes-related complica-tions and mortality in T2DM patients.Combined training and high-intensity training seemed to be better.Profes-sionally supervised PA was more effective.Conclusions Regular and multimodal PA is effective on glycemic control,and cardiovascular and metabolic risk factors in T2DM patients.It is advocated an individualized,diversified,adequately dosed(encouraging higher total dos-es),intensity-appropriate(promoting higher intensity),combined-mode and supervision-integrated PA strategies.