Apoptosis ; B7-H1 Antigen/genetics* ; Carcinoma, Non-Small-Cell Lung/genetics* ; Cost-Benefit Analysis ; Humans ; Immune Checkpoint Inhibitors ; Immunotherapy ; Ligands ; Lung Neoplasms/genetics*

Immunotherapy has opened a new era in cancer treatment. Drugs represented by immune checkpoint inhibitors have led to important breakthroughs in the treatment of various solid tumors, greatly improving the survival rate of cancer patients. Many types of immunotherapeutic drugs have become widely available; however, their efficacy is variable, and relatively few patients with advanced cancer experience life-altering durable survival, reflecting the complex and highly regulated nature of the immune system. The research field of cancer immunotherapy (CIT) still faces many challenges in pursuing the broader social goal of "curing cancer." Increasing attention has been paid to strengthening the understanding of the molecular or cellular drivers of resistance to immunotherapy, actively exploring more effective therapeutic targets, and developing combination therapy strategies. Here, we review the key challenges that have emerged in the era of CIT and the possible solutions or development directions to overcome these difficulties, providing relevant references for basic research and the development of modified clinical treatment regimens.
Combined Modality Therapy ; Humans ; Immunologic Factors ; Immunotherapy ; Neoplasms/therapy*

BACKGROUNDThe correlation between angiographic or intravascular ultrasound (IVUS) variables and fractional flow reserve (FFR) in patients with single left anterior descending artery (LAD) lesion has not been studied. The current study aimed at determining the best cutoff value of angiographic and IVUS parameters for defining FFR < 0.80 in patients with LAD lesion.

METHODSQuantitative coronary analysis, IVUS and FFR measurements were undergone in 169 patients with single LAD lesion. The best angiographic and IVUS cutoff value and their predictive value for FFR < 0.80 were compared using area under the receiver-operator characteristic curve (AUC) in overall patients or in subgroups stratified by lesion sites.

RESULTSFFR < 0.80 was found in 99 lesions (58.6%). Minimal lumen area (MLA), and plaque burden (PB) were two predictors of FFR < 0.80. Lesion length had less value in predicting FFR < 0.80. The cutoff value of PB and MLA for FFR < 0.80 was 75.4% and 3.03 mm(2). MLA and PB had similar high diagnostic value for proximal (cutoff value 3.04 mm(2) and 76.5%) and distal LAD lesion (2.82 mm(2) and 80.6%). Combination of MLA (2.82 mm(2)) and PB (80.6%) had increased diagnostic value for distal LAD lesion.

CONCLUSIONSMLA and plaque burden had equivalent diagnostic value for FFR < 0.80 when lesion localized in LAD. The predictive value of combination of MLA and plaque burden for distal LAD lesion was strengthened.

Coronary Angiography ; methods ; Coronary Artery Disease ; diagnostic imaging ; Coronary Vessels ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Plaque, Atherosclerotic ; diagnostic imaging ; Ultrasonography, Interventional ; methods

AIMTo study the mechanism of ginsenosides Rg1 and Rb1 promoting glutamic acid release from PC12 cells.

METHODSThe amount of glutamic acid released from PC12 cells was measured by high performance liquid chromatography (HPLC). The effect of Rg1 and Rb1 on the phosphorylation of synapsins was detected with immunofluorescent staining and Western blotting.

RESULTSBoth Rg1 (10 micromol x L(-1)) and Rb1 (10 micromol x L(-1)) increased glutamic acid release from PC12 cells. The release of glutamic acid was decreased by pre-incubating with the PKA inhibitor H89. H89 inhibited the release of glutamic acid induced by Rb1, but had no effect on the release of glutamic acid induced by Rg1. Moreover, Rb1 enhanced the phosphorylation of synapsins via PKA pathway, Rg1 was out of touch with this.

CONCLUSIONRb1 may promote release of neurotransmitters by increasing the phosphorylation of synapsins via PKA pathway, whereas the up-regulation of neurotransmitters release induced by Rg1 is independent of the phosphorylation of synapsins.

Animals ; Blotting, Western ; Cyclic AMP-Dependent Protein Kinases ; physiology ; Fluorescent Antibody Technique ; Ginsenosides ; pharmacology ; Glutamic Acid ; secretion ; Isoquinolines ; pharmacology ; Neurotransmitter Agents ; secretion ; PC12 Cells ; Phosphorylation ; Rats ; Sulfonamides ; pharmacology ; Synapsins ; metabolism

BACKGROUNDThe gender-based differences in adverse events after drug-eluting stent (DES) implantation between Chinese women and men have not been fully studied. The present study aimed to compare the 5-year clinical outcome after DES implantation in Chinese women and men.

METHODSChinese women (n = 298) and men (n = 698) with newly diagnosed de novo coronary lesions were studied after DES implantation. The primary endpoint was the occurrence of major adverse cardiac events (MACEs) over a 5-year follow-up, including myocardial infarction (MI), cardiac death, and target vessel revascularization (TVR). Propensity score matching (PSM) was used to compare the adjusted MACE rates between sexes.

RESULTSWomen differed in body habitus and had increased fasting cholesterol. Fewer women presented with MI, and they had better cardiac function with less complex disease. The unadjusted rate of MI at 3 years (2.1%) and 5 years (5.0%) and MACE (25.2%) at 5 years in men was significantly higher than that of women (0.3%, 1.0% and 17.8%, P = 0.050, P = 0.032, and P = 0.011, respectively). After PSM, the adjusted adverse events between sexes were similar. The stent thrombosis rate rapidly increased after 2 years in men.

CONCLUSIONSThere were significant gender-based differences in baseline characteristics. Chinese men had equivalent outcomes to women after DES after adjustment by PSM. The increased rate of MI in men was attributed to an increased unadjusted rate of MACE.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; therapy ; Prospective Studies ; Treatment Outcome

BACKGROUNDThe double kissing (DK) crush technique is a modified version of the crush technique. It is specifically designed to increase the success rate of the final kissing balloon post-dilatation, but its efficacy and safety remain unclear.

METHODSData were obtained from the DKCRUSH-I trial, a prospective, randomized, multi-center study to evaluate safety and efficacy. Post-procedural and eight-month follow-up intravascular ultrasound (IVUS) analysis was available in 61 cases. Volumetric analysis using Simpson's method within the Taxus stent, and cross-sectional analysis at the five sites of the main vessel (MV) and three sites of the side branch (SB) were performed. Impact of the bifurcation angle on stent expansion at the carina was also evaluated.

RESULTSStent expansion in the SB ostium was significantly less in the classical crush group ((53.81 ± 13.51)%) than in the DK crush group ((72.27 ± 11.46)%) (P = 0.04). For the MV, the incidence of incomplete crush was 41.9% in the DK group and 70.0% in the classical group (P = 0.03). The percentage of neointimal area at the ostium had a tendency to be smaller in the DK group compared with the classical group ((16.4 ± 19.2)% vs. (22.8 ± 27.1)%, P = 0.06). The optimal threshold of post-procedural minimum stent area (MSA) to predict follow-up minimum lumen area (MLA) < 4.0 mm(2) at the SB ostium was 4.55 mm(2), yielding an area under the curve of 0.80 (95% confidence interval: 0.61 to 0.92).

CONCLUSIONOur data suggest that the DK crush technique is associated with improved quality of the final kissing balloon inflation (FKBI) and had smaller optimal cutoff value of post-procedural MSA at the SB ostium.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Disease ; diagnostic imaging ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Ultrasonography

BACKGROUNDFractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is associated with fewer unfavorable events. However, the hemodynamic change in FFR after different stenting approaches for bifurcation lesions is still not fully studied. The aim of this study was to analyze the hemodynamic changes in FFR after double kissing (DK) crush and provisional side branch (SB) stenting (PS) for true coronary bifurcation lesions.

METHODSSeventy-five patients with true bifurcated lesions were randomly divided into DK (n = 38) and PS (n = 37) groups. Additional SB stenting in the PS group was required if there was any pinched SB ostium > 70% stenosis, or ≥ type B dissection, or TIMI flow < grade 3. FFR at hyperemia in the main vessel (MV) and SB was measured prior- and post-stenting, and at 8 months follow-up.

RESULTSBaseline clinical, angiographic and lesion characteristics were matched well between the two groups, with the exception of the final kissing balloon inflation (FKBI, 100.0% in the DK vs. 83.8% in the PS group, P < 0.001). Baseline FFR was comparable between the DK and the PS groups, however, the acute gain and late loss of SB FFR at 8-month follow-up in the DK group were 0.18 ± 0.15 and -0.06 ± 0.11, compared to 0.12 ± 0.18 (P = 0.044) and -0.002 ± 0.07 (P = 0.037) in the PS group, respectively. MV FFR post-stenting > 0.94 was seen in about 40% of patients. There was no significant difference in the clinical events at 1-year follow-up between the two groups.

CONCLUSIONSDK crush was associated with improved acute gain and late loss of SB FFR. The lower rate of FFR > 0.94 after stenting underscored the further improvement of stenting quality.

Adolescent ; Adult ; Aged ; Angioplasty, Balloon, Coronary ; Coronary Artery Disease ; therapy ; Coronary Stenosis ; therapy ; Drug-Eluting Stents ; Female ; Hemodynamics ; physiology ; Humans ; Male ; Middle Aged ; Percutaneous Coronary Intervention ; methods ; Treatment Outcome ; Young Adult

BACKGROUNDStenting strategies and clinical outcomes of bifurcation lesions in a chronic total occlusion (CTO) vessel after successful recanalization remain to be unknown.

METHODSBetween January 2001 and December 2009, 195 (41.1%) patients with 254 (47.0%) bifurcation lesions in CTO vessels from a pool of 564 patients with 659 CTO lesions were included and divided into proximal (n = 134) and distal (n = 120) groups, according to the location of the bifurcation lesions. The primary endpoint was the occurrence of major adverse cardiac events (MACE) at the end of clinical follow-up, including cardiac death, myocardial infarction, or target vessel revascularization (TVR).

RESULTSCollaterals with Rentrop class 3 were seen more in distal group (100% and 68.3%), compared to proximal group (76.9% and 45.6%). Two-stent technique for proximal bifurcation lesions was used in 24.6%, significantly different from the distal group (6.7%, P < 0.001), without significant difference in composite MACE between proximal and distal groups, or between one- and two-stent subgroups in proximal group. The composite MACE after 1-year in complete revascularization subgroup was 17.9% relative to 29.6% in the incomplete revascularization group (P = 0.044). Stents in long false lumen in main vessel were mainly attributive to decreased TIMI grade flow, with resultant increased in-stent restenosis, total occlusion, TVR and coronary aneurysms. Imcomplete revasculzarization (HR 2.028, P = 0.049, 95%CI 1.002 - 4.105) and post-stenting TIMI flow (HR 6.122, P = 0.020, 95%CI 1.334 - 28.092) were two independent predictors of composite MACE at the 1-year follow-up.

CONCLUSIONSTwo-stent was more used for proximal bifurcation lesions. No significant difference was observed in MACE between proximal and distal, or between one- and two-stent subgroups in the proximal group. Placement of a safety wire was critical for proximal bifurcation lesions. Complete revascularization was mandatory to improve clinical outcomes.

Aged ; Angioplasty, Balloon, Coronary ; adverse effects ; Coronary Stenosis ; therapy ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Registries ; Stents ; adverse effects ; Treatment Outcome

OBJECTIVETo compare the clinical effect of postoperative arterial infusion chemotherapy and systemic chemotherapy in gastric cancer.

METHODSFrom July 1997 to July 2002, the patients undergoing radical gastric resection were randomly divided into two groups, and received systemic or arterial infusion chemotherapy three weeks after radical resection. Systemic chemotherapy was carried out for two courses with 5-fluorouracil (5-FU), pirarubicin (THP), and mitomycin (MMC) administered according to FAM program, while arterial infusion chemotherapy for four courses with the same anticancer drugs infused via the celiac artery. The outcomes were compared.

RESULTSSystemic chemotherapy was carried out in 188 cases, and arterial infusion chemotherapy in 180 cases. There were no significant differences in sex, age, tumor location, histological type, TNM stage and surgical procedure between the two groups (P > 0.05). The 1, 3, 5 year survival rates were 87.2%, 53.7% and 43.1% in systemic chemotherapy, and 93.3%, 72.2% and 53.6% in arterial infusion chemotherapy respectively (P< 0.01).

CONCLUSIONThe survival rate of the patients with arterial infusion chemotherapy is higher than that with systemic chemotherapy, which indicates that arterial infusion chemotherapy can remarkably improve the prognosis of the patients with gastric cancer.

Adult ; Aged ; Chemotherapy, Cancer, Regional Perfusion ; methods ; Female ; Humans ; Infusions, Intra-Arterial ; Infusions, Intravenous ; Male ; Middle Aged ; Postoperative Period ; Stomach Neoplasms ; drug therapy

Aged ; Angina, Unstable ; pathology ; therapy ; Angioplasty, Balloon, Coronary ; methods ; Coronary Angiography ; Coronary Disease ; pathology ; therapy ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Prospective Studies ; Treatment Outcome