Objective:To explore the correlation between frailty and carotid plaque stability in patients with ischemic stroke.Methods:This study was a cross-sectional study. From May to December 2023, convenience sampling was used to select 360 patients with ischemic stroke in the Department of Neurology of Affiliated Hospital of Jining Medical University and underwent carotid artery color Doppler ultrasound examination as the study subject. Patients were surveyed using the General Information Questionnaire, Barthel Index and the Edmonton Frail Scale. Carotid artery color Doppler ultrasound was used to evaluate the stability of carotid plaques in patients. Multivariate Logistic regression was used to explore the correlation between frailty and carotid plaque stability.Results:A total of 360 questionnaires were distributed, and 352 valid questionnaires were collected, with a valid response rate of 97.78%. The incidence of frailty in 352 ischemic stroke patients was 44.89% (158/352). Multivariate analysis showed that compared to stable plaques, unstable carotid plaques were an independent risk factor for frailty in patients with ischemic stroke ( OR=2.127, 95% confidence interval: 1.247-3.626) . Conclusions:Compared to stable plaques, unstable carotid plaques increase the risk of frailty in patients with ischemic stroke. Strengthening the assessment of carotid plaques in patients with ischemic stroke by nursing staff can early identify high-risk individuals for frailty, and timely carry out personalized interventions, thereby reducing the occurrence of adverse health events in patients.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Objective:To discuss the therapeutic effect of resveratrol on the temporomandibular joint osteoarthritis(TMJOA),and to clarify the related mechanism.Methods:Forty-five SD rats were randomly divided into control group,model group,and resveratrol group,and there were 15 rats in each group.The rats in model group and resveratrol group were intra-articularly injected with 50 μL of 20 g·L-1 monosodium iodoacetate(MIA)to set TMJOA rat models,while the rats in control group were injected with an equal volume of normal saline.Three weeks after modeling,the rats in resveratrol group received an injection of 80 μL resveratrol solution,once a week for three weeks,while the rats in control and model groups were injected with an equal volume of normal saline.Micro-computed tomography(Micro-CT)system was used to detect the condyle structure and the bone volume fraction(BV/TV),trabecular thickness(Tb.Th),trabecular spacing(Tb.Sp),and trabecular number(Tb.N)of the rats in various groups were calculated;HE staining and toluidine blue staining were used to observe the pathomorphology of temporomandibular joint(TMJ)tissue of the rats in various groups;immunohistochemistry was used to detect the expression levels of SRY-related HMG box(SOX)-9,matrix metalloproteinase(MMP)-13,silent information regulator(Sirt)1,phosphatidylinositol 3-kinase(PI3K),phosphorylated protein kinase B(p-Akt),and phosphorylated mammalian target of rapamycin(p-mTOR)in TMJ tissue of the rats in various groups;real-time quantitative PCR(RT-qPCR)method was used to detect the expression levels of SOX-9,MMP-13,Sirt1,PI3K,mTOR,and Akt mRNA in TMJ tissue of the rats in various groups.Results:Three weeks after modeling,condylar bone was destructed,the surface was roughness,and continuity interruption were observed,indicating TMJOA model of the rats was established successfully.The Micro-CT system results showed that the condylar surface of the rats in control group was smooth and regularly shaped,with continuous bone texture;the rats in model group had significant condylar destruction,disrupted continuity,surface roughness,and varying degrees of bone defects;the rats in resveratrol group showed alleviated condylar lesions and improved appearance.Compared with control group,the BV/TV and Tb.Th of the rats in model group were significantly decreased(P<0.05),and Tb.Sp was significantly increased(P<0.05);compared with model group,the BV/TV and Tb.Th of the rats in resveratrol group were significantly increased(P<0.05),and the Tb.Sp was significantly decreased(P<0.05).The HE staining results showed clear layers and orderly chondrocyte arrangement in condyle of the rats in control group;the rats in model group showed rough uneven surface,obvious defects,and typical TMJOA features;the rats in resveratrol group showed slightly rough surface with generally clear layers and orderly arranged cells.The toluidine blue staining results showed distinct blue-purple staining of chondrocytes in hypertrophic layer of the rats in control group;pale staining or even loss of staining in some areas of the rats in model group;and distinct and relatively uniform staining in hypertrophic layer of the rats in resveratrol group.The immunohistochemistry results showed that compared with control group,the expression levels of MMP-13,PI3K,p-Akt,and p-mTOR proteins in TMJ tissue of the rats in model group were significantly increased(P<0.05),while the expression levels of SOX-9 and Sirt1 proteins in TMJ tissue of the rats were significantly decreased(P<0.05);compared with model group,the expression levels of SOX-9 and Sirt1 proteins in TMJ tissue of the rats in resveratrol group were significantly increased(P<0.05),whereas the expression levels of MMP-13,PI3K,p-Akt,and p-mTOR proteins were significantly decreased(P<0.05).The RT-qPCR results showed that compared with control group,the expression levels of MMP-13,PI3K,Akt,and mTOR mRNA in TMJ tissue of the rats in model group were significantly increased(P<0.05),while the expression levels of SOX-9 and Sirt1 mRNA were significantly decreased(P<0.05);compared with model group,the expression levels of SOX-9 and Sirt1 mRNA in TMJ tissue of the rats in resveratrol group were significantly increased(P<0.05),whereas the expression levels of MMP-13,PI3K,Akt,and mTOR mRNA were significantly decreased(P<0.05).Conclusion:Resveratrol has therapeutic effect on TMJOA,and its mechanism may be related to the activation of Sirt1 and inhibition of the PI3K-Akt-mTOR signaling pathway.

Objective:To screen risk factors for carotid plaque vulnerability in patients with ischemic stroke and construct a risk prediction model.Methods:From November 2019 to January 2021, a total of 164 patients with ischemic stroke hospitalized in the Neurology Department of the Affiliated Hospital of Jining Medical University were selected as the study subjects by convenience sampling method. Color doppler ultrasound was used to measure carotid plaques in patients with ischemic stroke to determine whether they were vulnerable plaques. The patients were surveyed using the General Information Questionnaire and the Type D Personality Scale. Binary Logistic regression analysis was used to explore the risk factors of carotid plaque vulnerability in ischemic stroke patients, and based on this, a risk prediction model for carotid plaque vulnerability in ischemic stroke patients was constructed.Results:A total of 87 patients with ischemic stroke had vulnerable carotid plaques. The results of binary Logistic regression analysis showed that age ( OR=1.136, 95% CI: 1.052-1.226), total score of Type D Personality Scale ( OR=1.170, 95% CI: 1.043-1.312), smoking history ( OR=3.058, 95% CI: 1.054-8.875), homocysteine ( OR=1.400, 95% CI: 1.179-1.664), triglycerides ( OR=2.356, 95% CI: 1.534-3.619) were risk factors for carotid plaque vulnerability in stroke patients ( P<0.05). The results of risk prediction model based on risk factors show that, the area under the receiver operating characteristic of the subjects was 0.935, indicating good clinical predictive ability. Conclusions:Age, total score of Type D Personality Scale, smoking history, homocysteine and triglyceride are risk factors of carotid plaque vulnerability in stroke patients. The risk prediction model can early identify and screen high-risk factors for carotid plaque vulnerability in ischemic stroke patients, and is worthy of clinical promotion and practice.

Objective:To investigate the efficacy of different treatment modes for locoregional recurrence after nephrectomy in patients with renal cell carcinoma.Methods:A total of 106 patients with locoregional recurrence after nephrectomy without distant metastasis (77 males and 29 females) admitted to Sun Yat-sen University Cancer Center from October 2001 to July 2020 were retrospectively analyzed. The median age was 51 (40, 60) years old. Radical nephrectomy was performed in 90 patients with primary tumor and partial nephrectomy was performed in 16 patients. Pathological diagnosis showed that 54 cases were clear cell carcinoma and 52 cases were non-clear cell carcinoma. 53 cases were in stage T 1-2 and 53 cases in stage T 3-4. The median diameter of recurrent lesions was 3.2 (2.0, 6.3) cm, and the median number was 2 (1, 4). The recurrence sites were divided into renal fossa recurrence (33 cases), renal fossa±retroperitoneal lymph node recurrence (38 cases), and intra-abdominal spread (35 cases). The median duration from primary surgery to local recurrence was 14.8 (7.3, 35.8) months. Two treatment groups were identified as systemic therapy alone (Group A) and local therapy with or without systemic therapy (Group B). The Kaplan-Meier method was used to compare the progression free survival (PFS) and overall survival (OS) between Group A and Group B. The Cox model was used to perform univariate and multivariate analysis. Results:Of all the 106 patients, 33 patients were in Group A and 73 patients were in Group B. In Group A, 29 patients (87.9%) received targeted therapy, and 4 patients (12.1%) received targeted therapy combined with immunotherapy. In Group B, 34 patients (46.6%) received surgery or ablation and 39 patients (53.4%) received SBRT, of which 62 patients (84.9%) received concurrent systemic therapy. Among them, 58 patients (93.5%) received targeted therapy, and 4 patients (6.5%) received targeted therapy combined with immunotherapy. The median follow-up period was 29.0 (15.4, 45.9) months, 64 patients progressed on tumor including 28 patients died. The median PFS and OS were 15.6 (7.1, 35.2) months and 66.9 (37.8, not reached) months. The median PFS of Group A and Group B were 7.6(5.0, 17.2)months and 22.2(9.6, 63.9)months respectively ( P=0.001), median OS of Group A and Group B were 45.7 (23.4, 62.8)months and 71.0(50.6, not reached)months respectively, and the 2-year OS were 70.6% and 85.5% in Group A and Group B respectively ( P=0.023). The univariate analysis showed local therapy with or without systemic therapy was significantly reduced 56% risk of tumor progression ( HR=0.44, P=0.003) and reduced 60% risk of death ( HR=0.40, P=0.028). The multivariate analysis showed that the OS was associated with ECOG score( HR=10.20, 95% CI 4.13-25.30, P<0.001)and local therapy( HR=0.23, 95% CI 0.09-0.58, P=0.002). Conclusion:Compared with systemic therapy alone, local therapy with or without systemic therapy can effectively improve the PFS and OS of patients with locoregional recurrence after nephrectomy.

Objective:To compare the effects of auricular point intradermal needling with auricular point sticking on digestive symptoms and quality of life in patients undergoing platinum-based chemotherapy regimens. Methods:Ninety-six patients receiving platinum-based chemotherapy were randomly assigned to three groups using the random number table method,with 32 cases in each group.The control group received conventional nursing care plus 5-hydroxytryptamine receptor antagonist,and the other two groups received additional auricular point intradermal needling or sticking.For the three groups of participants,the acute and delayed vomiting and nausea severity,quality of life,and the additional antiemetic consumption rate were observed. Results:The three groups had no significant differences in the acute vomiting frequency and nausea severity and appetite(P>0.05)but had significant differences in the delayed vomiting frequency and nausea severity(P<0.05);the auricular point intradermal needling group won over the auricular point sticking group.The three groups showed significant differences in comparing the appetite in the delayed stage(P<0.05);both auricular point intradermal needling and sticking groups showed advantages over the control group(P<0.05),but no significant difference existed between the auricular point intradermal needling and sticking groups(P>0.05).There were significant differences in comparing the functional living index-emesis(FLIE)score in both acute and delayed stages among the three groups(P<0.05)and the result favored the auricular point intradermal needling group over the auricular point sticking group(P<0.05).The additional antiemetic consumption rate was higher in the control group than in the other groups(P<0.05). Conclusion:Based on the conventional nursing and 5-hydroxytryptamine receptor antagonist,adding either auricular point intradermal needling or auricular point sticking can lower the vomiting frequency and nausea severity in the delayed stage and improve appetite in patients receiving platinum-based chemotherapy regimen,but they have no notable impact on digestive symptoms in the acute stage;auricular point intradermal needling is superior to auricular point sticking in comparing the overall efficacy.Both auricular point intradermal needling and auricular point sticking can enhance the quality of life in patients undergoing chemotherapy and reduce their additional antiemetic consumption.

Objective:To demonstrate the concept of planning target volume (PTV) is not suitable for intensity proton therapy (IMPT) in lung cancer, plan differences were compared based on the concept of PTV and Internal target volume (ITV), aiming to provide clinical reference.Methods:Six patients were retrospectively selected and approved by the local ethics committee. Each of the six patients received two IMPT plans based on a synchronous accelerator model, developed by SINAP team (Shanghai Institute of Applied Physics, China Academy Science University) and commercial treatment system: one with the PTV-based robust IMPT (PTV-IMPT) plan and the other with ITV-based robust IMPT (ITV-IMPT) plan. Three beams were set in all plans, and the final dose was calculated using Monte Carlo dose algorithm. The plan quality and robustness of PTV-IMPT and ITV-IMPT plans were evaluated quantitatively.Results:Compared to the PTV-IMPT plan, ITV-IMPT plan showed better target conformity index (conformability index: 0.58 vs.0.43), better homogeneity index (homogeneity index: 0.96 vs.0.92), lower V 5Gy in normal lung tissue (13.1% vs.13.5%) and maximum dose in spinal cord (8.9 Gy vs. 9.5 Gy) as well as plan monitor unit (MU: 338 vs. 401) . In addition, ITV-IMPT plan showed more robust in target coverage (0.003-0.032 vs. 0.02-0.28), and normal lung tissue was also found a bit robust in the ITV-IMPT plan ( 0.06-0.11, 0.07-0.13). Conclusions:Compared with the PTV-IMPT plan, ITV-IMPT plan has the advantages of high planning quality, well robustness and better tumor motion mitigation. Therefore, ITV concept is recommended to be applied in the IMPT plan for lung cancer.

Objective: To report the experience on the multi-disciplinary management of metastatic renal cell (mRCC) patients in a single center. Methods: Data of 168 mRCC patients treated by multi-disciplinary team (MDT) at Sun Yat-sen University Cancer Center from December 2007 to February 2019 was retrospectively analyzed.Three treatment groups were identified, including 76 patients with 55 males and 21 females, received anti-angiogenic agents alone (Group A), 66 patients with 55 males and 11 males, received anti-angiogenic agents plus local therapy (Group B)and 26 patients, with 19 males and 7 females, received anti-angiogenic agents plus immunotherapy and local therapy (Group C). The Sunitinib, Sorafenib, Axitinib were chosen for the TKI. The Pembrolizumab was used for immunotherapy. The stereotactic body radiation therapy and surgical excision were considered as the local therapy. The study aims to compare the age, gender, IMDC score, pathology, nbephrectomy, adverse events, progression-free survival and overall survival (OS). Results: Of all patients, the median follow-up duration was 23 months (ranging 6-117 cmonths). The PFS was 18.3 months and median OS was 33.5 months. The 2 years and 5 years survival rate was 66% and 35%, respectively. The median OS of Group A, B and C were 29.8 months, 44.6 months and not reached. 2y-OS was 58%, 67% and 89%, while 5y-OS 12%, 46% and 57%.There was no difference in age, gender, IMDC score, pathology, synchronous metastases or nephterectomy between the three groups. The prognostic result in TKI based combination therapy was superior to TKI therapy alone, which the 5y-OS was 51% and 11%, respectively. The prognostic result in group C's moderate-high risk mRCC patients was superior to group A and B. The median OS in TKI+ DC and CIK+ Pembrolizumab was 49.1 months and 53.1 months. On univariate analyses, IMDC score, nephrectomy and treatment group was associated with OS (P<0.05). On multivariate analyses, treatment group, nephrectomy was associated with OS (P<0.05). The risk of death of Group C decreased about 60% [HR 0.39 (0.17, 0.89), P=0.026]. 78 (46.4%) patients on TKI alone and 16 (61.5%) patients treated with TKI plus immunotherapy had Grade 3 or 4 adverse events. 16 (20.3%) patients had Clavien Ⅲ-Ⅳ toxicity after surgical procedures. 6 (5.7%) patients had Grade 3 toxiciy after SBRT. Conclusions Patients treated with combined therapy had better survival than those treated with anti-angiogenic agents alone. MDT approach could bring survival benefit to mRCC patients.

Objective:To evaluate the efficacy and safety of Tyrosine Kinase Inhibitors (TKIs) combined with stereotactic body radiation therapy(SBRT) in the treatment of renal cell carcinoma (RCC) patients with bone metastasis.Methods:The clinical data of 80 RCC patients with bone metastasis in Sun Yat-sen University Cancer Center from April 2010 to April 2020 were analyzed retrospectively. Among them, 64 patients were medium or high risk according to the International Metastatic Renal Cell Carcinoma Database Consortium(IMDC) score. Twenty-four patients received TKI therapy alone(Group A), and the other 56 cases received TKIs combined with SBRT to bone metastastic lesions (Group B).Results:The median follow-up period was 20.7 months (4.8-115.6 months), 70 patients received second or third-line targeted drug therapy, and 4 patients in group A and 15 patients in group B received TKI plus immunotherapy. Fifty-four patients had symptoms of bone pain before radiotherapy, 46 patients were satisfied with the analgesic effect after SBRT treatment. Twelve patients got complete response (CR) after bone lesions, and 32 patients achieved partial response (PR). Forty patients died of disease progression during follow-up. The median OS was: 20.7 months vs not reached(Group A vs. Group B), and the 2-y OS and 5-y OS were 50% vs. 62%, and 19% vs. 56%, respectively ( P=0.006). There were only 2 patients (3.6%) had grade 3 SBRT related adverse events. Conclusions:SBRT combined with TKIs improved the quality of life and prolonged the overall survival of RCC patients with bone metastasis.

Objective:To investigate the blood flow change status in early stage tumor-related areas of hepatocellular carcinoma and its clinical significance after radiofrequency ablation using multi-slice spiral CT whole-liver perfusion imaging technology.Methods:21 cases of primary liver cancer that underwent CT-guided radiofrequency ablation were included. CT perfusion scans were divided into four groups according to the time points of CT scans (before surgery, immediately after surgery and 1 and 3 month after surgery), and then blood perfusion parameters of the corresponding areas of the tumor were measured. Statistical analysis was performed using two independent samples of non-parametric Wilcoxon rank-sum test. The differences of blood perfusion parameters between tumor or ablation lesion and background liver parenchyma, paratumor tissue or inflammatory response zone were compared before, immediately and 1 and 3 months after surgery, respectively.Results:(1) The hepatic arterial perfusion (HAP) and hepatic arterial perfusion index (HPI) of cancerous liver tumors and background liver parenchyma was significantly increased ( P < 0.01). The total liver perfusion (TLP) was higher than the background liver parenchyma ( P = 0.01 < 0.05). The time to peak (TTP) was significantly lower than background liver parenchyma ( P < 0.01); (2) The perfusion parameters of HAP, PVP and TLP were lower than the background liver parenchyma in the complete ablation lesions immediately after radiofrequency ablation and 1 and 3 months after surgery, and the difference was statistically significant ( P < 0.05); (3) The inflammatory response zone of ablation lesions of HAP, HPI, and TLP were gradually decreased with the extended postoperative time and TTP was gradually increased, while PVP did not change significantly; (4) HAP, HPI, and TTP were compared between the tumor and the tumor inflammatory response zone immediately after surgery, and 1 and 3 months after surgery, and the difference was statistically significant ( P < 0.01). However, there was no statistically significant difference between PVP and TLP ( P > 0.05). Conclusion:CT whole-liver perfusion imaging can precisely evaluate the early stage blood flow change status in peritumor and tumors before and after radiofrequency ablation and then objectively evaluate tumor’s blood supply and therapeutic effect on hepatocellular carcinoma.