1.Efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with advanced hepatocellular carcinoma
Long CHENG ; Yue ZHANG ; Yushen LIU ; Zhaoqing DU ; Zhaoyang GUO ; Yangwei FAN ; Ting LI ; Xu GAO ; Enrui XIE ; Zixuan XING ; Wenhua WU ; Yinying WU ; Mingbo YANG ; Jie LI ; Yu ZHANG ; Wen KANG ; Wenjun WANG ; Fanpu JI ; Jiang GUO ; Ning GAO
Journal of Clinical Hepatology 2024;40(10):2034-2041
Objective To investigate the efficacy and safety of camrelizumab monoclonal antibody combined with molecular-targeted therapy in elderly patients with unresectable or advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the patients with unresectable/advanced HCC who attended six hospitals from January 1,2019 to March 31,2021,and all patients received camrelizumab monoclonal antibody treatment,among whom 84.8%also received targeted therapy.According to the age of the patients,they were divided into elderly group(≥65 years)and non-elderly group(<65 years).The two groups were assessed in terms of overall survival(OS),progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),and immune-related adverse events(irAE).The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups;the independent samples t-test was used for comparison of normally distributed continuous data,and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups.The Kaplan-Meier method was used for survival analysis,and the log-rank test was used for comparison of survival curves.Univariate and multivariate Cox proportional hazards regression analyses were used to determine the independent influencing factors for PFS and DCR at 6 months.Results A total of 99 HCC patients were enrolled,with 27 in the elderly group and 72 in the non-elderly group.The elderly group had an OS rate of 67.8%,an ORR of 44.4%,and a DCR of 74.1%at 12 months and a median PFS of 6.4(95%confidence interval[CI]:3.0-12.4)months,with no significant differences compared with the non-elderly group(all P>0.05).The median OS was unavailable for the elderly group,while the non-elderly group had an OS of 18.9(95%CI:13.0-24.8)months;there was no significant difference between the two groups(P=0.485).The univariate and multivariate Cox regression analyses showed that major vascular invasion(MVI)was an independent risk factor for PFS(hazard ratio[HR]=2.603,95%CI:1.136-5.964,P=0.024)and DCR(HR=3.963,95%CI:1.671-9.397,P=0.002)at 6 months,while age,sex,etiology of HBV infection,presence of extrahepatic metastasis,Child-Pugh class B,and alpha-fetoprotein>400 ng/mL were not associated with PFS or DCR at 6 months.For the elderly group,the incidence rates of any irAE and grade 3/4 irAE were 51.9%and 25.9%,respectively,with no significant differences compared with the non-elderly group(P>0.05),and skin disease was the most common irAE in both groups(39.4%).Conclusion Camrelizumab monoclonal antibody combined with molecular-targeted therapy has similar efficacy and safety in patients with unresectable/advanced HCC aged≥65 years and those aged<65 years.MVI is associated with suboptimal response to immunotherapy and poor prognosis.
2.Expert consensus on clinical application of 177Lu-prostate specific membrane antigen radio-ligand therapy in prostate cancer
Guobing LIU ; Weihai ZHUO ; Yushen GU ; Zhi YANG ; Yue CHEN ; Wei FAN ; Jianming GUO ; Jian TAN ; Xiaohua ZHU ; Li HUO ; Xiaoli LAN ; Biao LI ; Weibing MIAO ; Shaoli SONG ; Hao XU ; Rong TIAN ; Quanyong LUO ; Feng WANG ; Xuemei WANG ; Aimin YANG ; Dong DAI ; Zhiyong DENG ; Jinhua ZHAO ; Xiaoliang CHEN ; Yan FAN ; Zairong GAO ; Xingmin HAN ; Ningyi JIANG ; Anren KUANG ; Yansong LIN ; Fugeng LIU ; Cen LOU ; Xinhui SU ; Lijun TANG ; Hui WANG ; Xinlu WANG ; Fuzhou YANG ; Hui YANG ; Xinming ZHAO ; Bo YANG ; Xiaodong HUANG ; Jiliang CHEN ; Sijin LI ; Jing WANG ; Yaming LI ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2024;31(5):844-850,封3
177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.
3.Expert consensus on operational guideline for 68Ga-DOTATATE/18F-FDG two-day total-body PET/CT imaging of neuroendocrine neoplasms
Haojun YU ; Yushen GU ; Zhi YANG ; Ruimin WANG ; Hubing WU ; Xinming ZHAO ; Xiaohua ZHU ; Zhaoping CHENG ; Wei FAN ; Zhifang WU ; Sijin LI ; Hongcheng SHI
Chinese Journal of Clinical Medicine 2024;31(4):687-690,封3
68Ga-DOTATATE/18F-FDG two-day low-dose total-body PET/CT imaging is increasingly employed to facilitate the diagnosis,prognosis,and heterogeneity assessment of neuroendocrine neoplasms.We present a consensus on operational guideline for a two-day combined imaging from experts in low-dose/ultra-low-dose total-body PET/CT from several domestic medical institutions.
4.Sex hormone levels have little impact on outcomes of cardiac surgery in fertile women with congenital heart disease: A retrospective cohort study
Kaiyu WANG ; Yushen FANG ; Jianrui MA ; Haiyun YUAN ; Jian ZHUANG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(06):878-884
Objective To examine the influence of hormonal fluctuations on the perioperative outcomes of patients undergoing congenital heart surgery. Methods We conducted a retrospective analysis of clinical data from fertile women diagnosed with congenital heart disease at the Guangdong Provincial People's Hospital, between January 1, 2015, and July 30, 2019. Initially, patients were categorized into groups based on serum progesterone levels: a low progesterone group (n=31) and a high progesterone group (n=153). Furthermore, based on serum estrogen levels, they were divided into a low estrogen group (n=10), a medium estrogen group (n=32), and a high estrogen group (n=118) for comparative analysis. A control group (n=24) consisted of patients who received progesterone injections before their menstrual period. Results We finally included 184 patients. The patients’ average age was 27.6±5.7 years, with 142 (77.17%) presenting with complex congenital heart conditions. There were statistically significant differences in total postoperative standard thoracic drainage volume and postoperative albumin level between the high and low progesterone groups (P<0.05), while other perioperative outcome indicators showed no statistical differences (P>0.05). Among the different serum estrogen level groups, there were statistically significant differences in postoperative blood urea nitrogen levels, total postoperative standard thoracic drainage volume, and hospital stay (P<0.05), while other perioperative outcome indicators showed no statistical differences (P>0.05). Conclusion Considering the overall clinical significance, the physiological changes in sex hormone levels appear to have a negligible effect on the perioperative outcomes of fertile women with congenital heart disease.
5.Analysis of clinical data of necrotizing fasciitis secondary to intestinal fistulas and screening the mortality risk factors
Chenyuyao ZHAO ; Yushen ZHANG ; Zhanjie YANG ; Mingqing WANG ; Wenjun XUE ; Ran HUO ; Ran ZHAO
Chinese Journal of Burns 2024;40(2):141-150
Objective:To analyze the clinical data and to screen the mortality risk factors of necrotizing fasciitis (NF) secondary to intestinal fistulas (NFsIF).Methods:This study was a retrospective observational study. The data of all NFsIF cases who met the inclusion criteria and were admitted into Shandong Provincial Hospital Affiliated to Shandong First Medical University (hereinafter referred to as our unit) from January 2000 to October 2023, and in PubMed, Web of Science, Scopus, China National Knowledge Infrastructure, and Chinese Medical Journal Network databases from its establishment to October 2023 were retrieved and screened. Based on clinical outcomes, the cases were divided into survival group (47 males and 24 females) and death group (16 males and 7 females), and the mortality rate was calculated. Clinical data of patients in the two groups including age, underlying diseases (most related to NF), symptom duration before presentation, white blood cell count, causes of NF, signs of peritonitis, scope of NF involvement, and intestinal management and wound management measures were compared and analyzed to screen the risk factors of death in 94 patients with NFsIF.Results:A total of 94 valid cases were collected, including 90 patients reported in the literature and 4 patients admitted to our unit, with the mortality rate of patients being 24.5% (23/94). Univariate analysis showed that there were no statistically significant differences in age, underlying diseases, symptom duration before presentation, white blood cell count, causes of NF, signs of peritonitis, scope of NF involvement between patients in the two groups ( P>0.05); there were statistically significant differences in intestinal treatment and wound treatment between the two groups (with χ2 values of 17.97 and 8.33, respectively, P<0.05). Multivariate logistic regression analysis showed that both intestinal treatment measures and wound treatments measures were independent risk factors for death in 94 NFsIF patients, among which first-stage colostomy+late-stage reconstruction and negative presssure therapy had higher protective effects (with odds ratios of 0.05 and 0.27, respectively, 95% confidence intervals of 0.01-0.33 and 0.08-0.88, respectively, P<0.05). Conclusions:The mortality risk of patients with NFsIF is high. Based on comprehensive treatments, active intestinal and wound treatment may be the key to avoid death, with first-stage colostomy+late-stage reconstruction and negative pressure therapy having higher protective effects.
6.Application of breakthrough series quality improvement model in preventing blood flow infections related to non-cuffed catheters
Na CHEN ; Yushen REN ; Li TIAN ; Xiaoping WANG ; Yujun WANG ; Yanling SUN ; Hongwen MA ; Xiaohua YUAN
Chinese Journal of Practical Nursing 2024;40(21):1601-1607
Objective:To explore the application effect of breakthrough series (BTS) quality improvement model in the prevention of catheter-related bloodstream infection in hospitalized patients with indwelling non-cuffed catheter (NCC).Methods:Using a non synchronous pre and post control study method, convenience sampling was used to select NCC patients from four hospitals in Tianjin from January to September 2022 who received conventional nursing plans as the control group, and NCC patients from February to October 2023 who received nursing plans based on the BTS quality improvement model as the observation group. Compared the incidence of NCC related bloodstream infections between two groups of patients, the implementation of key preventive measures for NCC related bloodstream infections by nursing staff, and patient satisfaction.Results:Among the 984 patients included in the control group, there were 687 males and 297 females, aged (62.43 ± 13.77) years old; among the 959 patients included in the observation group, there were 651 males and 308 females, aged (61.96 ± 13.89) years old. After applying the improved model, the incidence of NCC related bloodstream infections in the observation group was 0.12‰ (1/8 676), lower than the control group′s 0.71‰ (7/9 827), and the difference was statistically significant ( χ 2=4.37, P<0.05) ;the implementation rate of key measures for preventing NCC related bloodstream infections in the observation group was 90.00% (54/60) for catheter outlet care and 91.67% (55/60) for maximizing sterile barrier, both higher than 70.37% (38/54) and 75.93% (41/54) in the control group, with statistical significance ( χ2=7.03, 5.30, both P<0.05); the total satisfaction rate of patients in the observation group was 92.91% (891/959), which was higher than 58.64% (577/984) in the control group, and the difference was statistically significant ( χ2=15.28, P<0.05). Conclusions:The implementation of BTS quality improvement model is helpful to improve the nursing quality of patients with indwelling NCC dialysis and improve the patient outcomes.
7.Anti-cutaneous squamous cell carcinoma effect and mechanism of dihydrochromone-spliced polycyclic pyrrole-spiroepoxidole compound 3m
Shanshan TANG ; Dongyun RONG ; Ye WANG ; Yushen SU ; Tao WANG ; Qiu LONG ; Yu CAO
China Pharmacy 2023;34(9):1086-1092
OBJECTIVE To study the effect and mechanism of dihydrochromone-spliced polycyclic pyrrole-spiroepoxidole compound 3m on cutaneous squamous cell carcinoma. METHODS Using human cutaneous squamous cell carcinoma A431 and Colo-16 cells as research subjects, CCK-8 assay was used to detect the effects of different concentrations of 3m (5, 10, 20, 40, 80 μmol/L) on the proliferation of A431 and Colo-16 cells after 24, 48 and 72 hours; the median inhibitory concentration (IC50) was calculated at 48 h of treatment. A431 and Colo-16 cells were divided into control group, 3m low-concentration and high- concentration groups (15, 30 μmol/L). After treated with relevant drugs or culture medium for 48 h, the morphological changes of cells in each group were observed by inverted microscope. Clone formation rate, migration rate and number of cell invasions, cell cycle distribution and apoptosis rate were detected. The phosphorylation, or expression of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway related proteins [JAK2, STAT3, B-cell lymphocyte-2 (Bcl-2), Bcl-2- associated X protein (Bax)], and their mRNA expression in cells were detected. RESULTS 3m could significantly inhibit the proliferation of A431 and Colo-16 cells after treated for 24, 48, 72 h (P<0.01), and IC50 of them were 20.36, 23.72 μmol/L, respectively. After 48 hours of treatment, compared with control group, A431 and Colo-16 cells arranged sparsely and loosely connected in 3m low-concentration and high-concentration groups. The clone formation rate, migration rate, number of cell invasions, mRNA expressions of JAK2, STAT3 and Bcl-2, the phosphorylation of JAK2 and STAT3, protein expression of Bcl-2 were significantly decreased/weakened (P<0.01). Proportion of cell cycle in G2 phase, apoptosis rate, protein and mRNA expression of Bax were increased significantly (P<0.01); and all the above effects were in dose-dependent manner. CONCLUSIONS 3m can inhibit the proliferation, clone formation, migration and invasion abilities of cutaneous squamous cell carcinoma A431 and Colo-16 cells in a dose-dependent manner, the mechanism of which may be associated with inhibiting the activity of JAK2/STAT3 signaling pathway, and inducing cell apoptosis.
8.The impact of childhood trauma on cognitive function in individuals with clinical high risk of psychosis
Yushen DING ; Fang DONG ; Wenpeng HOU ; Chuanyue WANG
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(8):688-693
Objective:To explore the impact of cognitive function and childhood trauma in individuals with clinical high risk of psychosis (CHR).Methods:From June 2017 to September 2022, a total of 62 individuals with CHR(CHR group) were screened by structured interviews with psychiatric risk syndrome (SIPS) at Beijing Anding Hospital, and 61 healthy controls(healthy control group) matched in gender, age, and educational years were recruited. All participants were evaluated by the childhood trauma questionnaire (CTQ) and the Chinese version of the MATRICS consensus cognitive test battery (MCCB). Differences in cognitive function and childhood trauma between the two groups were compared by R4.1.1 software, and the correlation between cognitive function and childhood trauma in the CHR group was analyzed.Results:The scores of MCCB composite score (41.46±6.97), information processing speed (40.20±8.40), attention vigilance (40.92±11.00), working memory (41.09±9.97), verbal learning, and visual learning of CHR group were significantly lower than those of healthy controls(MCCB composite score(46.26±7.64), information processing speed(45.83±8.36), attention vigilance(46.30±9.57), working memory(46.18±8.49)), and with statistically significant differences ( t=-3.73--2.03, P<0.05). The total CTQ score, emotional abuse, physical abuse, and physical neglect factor scores of the CHR group (40.0 (36.0, 50.8), 7.5 (6.0, 10.0), 5.0 (5.0, 7.0), 9.0 (7.0, 11.0)) were significantly higher than those of the healthy control group (34.0 (31.0, 40.0), 6.0 (5.0, 8.0), 5.0 (5.0, 6.0), 9.0 (6.0, 10.0) ) ( Z=-4.07--2.06, P<0.05). In the CHR group, the total score of childhood trauma and the score of physical abuse factors were negatively correlated with working memory ( r=-0.29, -0.28, P<0.05), and the total score of cognitive function, attention vigilance, and word learning were negatively correlated with physical neglect ( r=-0.28, -0.26, -0.31, P<0.05). After partial correlation analysis using gender, age, years of education, and total SIPS score as covariates, the aforementioned correlation remained significant. Conclusion:CHR individuals have multiple cognitive deficits, and childhood trauma is more serious. Childhood trauma, especially physical trauma, may affect the cognitive function of CHR individuals.
9.Study on the Effects and Its Mechanism of Sinapine Thiocyanate on the Proliferation ,Epithelial Mesenchymal Transition and Metastasis of Human Cutaneous Squamous Cell Carcinoma SCL- 1 Cells
Yushen SU ; Zhirui ZENG ; Dongyun RONG ; Ye WANG ; Dan LI ; Shanshan TANG ; Tao WANG ; Xuemei LONG ; Yu CAO
China Pharmacy 2021;32(8):952-960
OBJECTIVE:To stud y the effects of sinapine thiocyanate (ST) on the proliferation ,epithelial mesenchymal transformation(EMT)and metastasis of human cutaneous squamous cell carcinoma SCL- 1 cells,and to investigate its possible mechanism. METHODS :Human cutaneous squamous cell carcinoma SCL- 1 cells were divided into blank control group (0.1% DMSO) and ST different concentration groups (5,10,20 μmol/L). CCK- 8 assay,5-ethynyl-2′-deoxyuridine(EDU)test, scratch test and Transwell chamber invasion test were adopted to test the proliferation ,migration and invasion ability. The expression of N-cadherin and E-cadherin were detected by Western blot and immunofluorescence assay . Other SCL- 1 cells were collected and divided into blank control group (0.1% DMSO),ST group (20 μmol/L),ST+NSC228155 group [ 20 μmol/L ST+100 μmol/L NSC228155(EGFR agonist )] and ST+SC 79 group [ 20 μmol/L ST+20 μmol/L SC79(PI3K/Akt agonist )]. The proliferation ,migration and invasion ability of SCL- 1 cells in each group were detected by CCK- 8 assay,scratch test and Transwell chamber invasion assay. The expression of epidermal growth factor receptor (EGFR),phosphatidylinositol 3 kinase(PI3K),phosphorylated phosphatidylinositol 3 kinase(p-PI3k),protein kinase B (Akt)and phosphorylated protein Akt (p-Akt)protein of cells in blank control group and ST different concentration groups(5,10,20 μmol/L)were determined by Western blot assay so as to validate the relationship between ST effect and EGFR/ PI3K/Akt signaling pathway. SCL- 1 cells and human normal skin fibroblasts cell WS 1 were divided into blank control group (0.1% DMSO),ST group (20 μmol//L),ZD1839 group(positive control ,20 μmol//L,EGFR inhibitor )and LY 294002 group(positive control,20 μmol//L,PI3K/Akt inhibitor ). CCK- 8 assay was used to detect the cell proliferation in order to evaluate the cells cytotoxicity of ST. RESULTS :Compared with blank control group ,the proliferation ,migration and invasion ability of SCL- 1 cells were significantly decreased in 5,10,20 μmol/L ST groups(P<0.05). Western blot and immunofluorescence assay showed that the expression of N-cadherin in SCL- 1 cells were decreased significantly in 5,10,20 μmol/L ST groups(P<0.05),while the protein expression of E-cadherin was increased significantly (P<0.05);the protein expressions of EGFR ,p-PI3K and p-Akt were significantly decreased (P<0.05). Compared with ST group ,the proliferation ,migration and invasion ability of SCL- 1 cells were increased significantly in ST + NSC 228155 group and ST + SC 79 group (P<0.05). Compared with blank control group ,the proliferation ability of WS 1 cells had no significant change in ST group ,while the proliferation ability of SCL- 1 cells was decreased significantly (P<0.05);the proliferation ability of the two kinds of cells were decreased significantly in ZD 1839 group and LY 294002 group(P<0.05). Compared with ST group ,the proliferation ability of WS 1 cells was decreased significantly in ZD1839 group and LY 294002 group(P<0.05),but there was no significant difference in the proliferation ability of SCL- 1 cells (P>0.05). CONCLUSIONS :ST may inhibit the proliferation ,EMT and metastasis of SCL- 1 cells through inhibiting the activation of EGFR/PI 3K/Akt signaling pathway ,and its side effects are few.
10.Pharmacokinetics of ~(131)I-labeled-metuximab and transarterial chemoembolization for treatment of hepatocellular carcinoma
Jun MA ; Jianhua WANG ; Rong LIU ; Sheng QIAN ; Yi CHEN ; Hongcheng SHI ; Yushen GU
Chinese Journal of Radiology 2010;44(1):74-78
To study the pharmacokinetics of ~(131)I-Metuximab injection (Licartin) combined with transarterial chemoembolization (TACE) for treatment of hepatocellular carcinoma (HCC). MethodsLicartin (27.75 MBq/kg) and the mixture of anticancer drug and Lipiodol were sequentially administered with interval of 20 minutes to 15 patients with HCC via a transfemoral catheter.After the Licartin was administrated, the pharmacokinetic and biodistribution data were evaluated through venous blood samples,urine collections,and 4 γ-scintigraphies (SPECT) over 7 days. The pharmacokinetic parameters were determined from integration of the blood radioactivity-time curves using the SPSS 12.0 software. The tumor-no-tumor ratio (T/NT) was calculated by ROI. Absorbed doses in organ were estimated according to the medical internal radiation dose formalism. The biodistribution of licartin within patient's body at different time points was compared for various organs using analysis of variance for repeated measures, as well as the T/NT ratio. ResultsThe blood radioactivity-time curves followed the dynamics two-compartment model, with the major pharmacokinetic parameters including t_(1/2)α(1.96±1.65) h, and t_(1/2)α(19.07±5.91) h,and t_(1/2)β (57.09±10.92) h, and C_(max) 2.113×10~9min~(-1)·L~(-1), and AUC_(0-∞) 1.302×10~(11) h·min~(-1)·L~(-1), respectively. The accumulated urine radioactivity was 52.2% of administrated dosage during 144 h after administration. There were statistical significant difference of biodistribution of licartin and T/NT ratio between organs at different time points (F=6.583, P<0.01 and F=3.546, P<0.01). SPECT scans showed the significant accumulation of the radioconjugate in liver tumor and faint uptake in other organs for 14 days. Tumor-to-liver ratio decreased from 2.88±1.02 at 3 h to 1.64±0.40 at 168 h (n=7). Organ absorbed dose was (3.19±1.01) Gy in liver (n=12) and (0.55±0.09) Gy in red marrow (n=7). ConclusionLicartin combined with TACE for treatment of HCC is helpful to significantly accrete the radioconjugate in liver tumor, and protect normal organs from radiotoxictiy.

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