Objectives:Coronary slow flow(CSF)has long been regarded as a marker of coronary microvascular dysfunction(CMD).This study aims to evaluate the diagnostic value of CSF for CMD in patients with angina and nonobstructive coronary arteries(ANOCA).Methods:The study data were derived from the ANOCA-CMD prospective cohort study.All enrolled patients underwent coronary angiography and concurrent coronary physiological assessments in the left anterior descending artery using pressure-wire and thermodilution techniques to obtain coronary flow reserve(CFR)and the index of microcirculatory resistance(IMR).Based on the results,CMD was classified into four subtypes:CMD with elevated IMR(IMR≥25),CMD with reduced CFR(CFR<2.5),CMD with either reduced CFR or elevated IMR(CFR<2.5 or IMR≥25),and CMD with both reduced CFR and elevated IMR(CFR<2.5 and IMR≥25).The corrected thrombolysis in myocardial infarction(TIMI)frame count(CTFC)in the left anterior descending artery was calculated from coronary angiography images,with CSF defined as CTFC>27.This study evaluated the correlation between CTFC,CFR,and IMR,and investigated the diagnostic value of CSF for CMD in ANOCA patients.Results:A total of 103 ANOCA patients were enrolled in this study,with a mean age of(64.2±10.6)years,and 53.4％were female.Among them,57 patients(55.3％)were diagnosed with coronary slow flow.Patients with slow flow had higher IMR(P<0.001)and CFR(P=0.041).Similarly,the proportion of CMD with elevated IMR was higher in the slow flow group(P<0.001),while the proportion of CMD with reduced CFR was lower(P=0.044).There was no significant difference between the groups in the proportions of CMD with either reduced CFR or elevated IMR or CMD with both reduced CFR and elevated IMR(all P>0.05).CTFC was positively correlated with hyperemic mean transit time(r=0.424,P<0.001),IMR(r=0.430,P<0.001),and CFR(r=0.211,P=0.032).The area under the curve(AUC)of CTFC for diagnosing CMD with elevated IMR was 0.721(95％CI:0.623-0.819)with an accuracy of 67％(57％,76％),for diagnosing CMD with reduced CFR was 0.610(95％CI:0.499-0.720)with an accuracy of 60％(50％,70％),for diagnosing CMD with either reduced CFR or elevated IMR was 0.549(95％CI:0.425-0.673)with an accuracy of 47％(37％,57％),and for diagnosing CMD with both reduced CFR and elevated IMR was 0.582(95％CI:0.471-0.693)with an accuracy of 47％(37％,57％).Thus,CSF demonstrated limited diagnostic values across all subtypes of CMD.Conclusions:In ANOCA patients,CSF cannot serve as an effective diagnostic marker for CMD.Therefore,in clinical practice,the slow flow phenomenon should not be directly equated with the presence of coronary microvascular dysfunction in ANOCA patients.

Objective:Investigate the impact of calcification on the long-term outcomes of patients with coronary chronic total occlusion (CTO) after percutaneous coronary intervention (PCI).Methods:A retrospective cohort study was conducted. Patients who underwent PCI and had at least one CTO lesion at Fuwai Hospital between January 2010 and December 2013 were consecutively enrolled. Calcification was evaluated by coronary angiography, and patients were divided into two groups: moderate/severe calcification group and non/mild calcification group. Clinical follow-up was completed up to 5 years. Incidence of PCI-related complications and immediate procedural outcomes were compared between two groups, and the primary endpoint was the target lesion failure (TLF) at 5 years after PCI. Clinical follow-up endpoint events were analyzed using Kaplan-Meier survival analysis with log-rank test, and Cox multivariate regression model was used to evaluate the relationship between calcification and TLF.Results:The study included 2 659 CTO patients with an age of (57.2±10.5) years, of whom 442 (16.6%) were female, and among whom 13.5% (360/2 659) had moderate/severe calcification. Compared with the non/mild calcification group, the moderate/severe calcification group had a higher incidence of PCI-related complications (43.2% (156/361) vs. 32.5% (772/2 374), P<0.001) and procedural failure (34.3% (124/361) vs. 24.3% (577/2 374), P<0.001). Additionally, the moderate/severe calcification group showed a higher risk of the primary endpoint event (TLF) during the 5-year follow-up (19.8% vs. 15.3%, log-rank P=0.028). Higher incidence of cardiac death was observed in moderate/severe calcification group (5.7% vs. 2.7%, log-rank P=0.003). Cox multivariate regression analysis revealed that moderate/severe calcified plaques remained an independent risk factor for 5-year TLF after CTO-PCI ( HR=1.34, 95% CI: 1.01-1.79, P=0.043). Conclusion:Compared with CTO patients with non/mild calcification, those with moderate/severe calcification have higher procedural failure and complication rates, as well as poorer long-term prognosis, mainly due to an increase in cardiac death.

Objectives:Coronary slow flow(CSF)has long been regarded as a marker of coronary microvascular dysfunction(CMD).This study aims to evaluate the diagnostic value of CSF for CMD in patients with angina and nonobstructive coronary arteries(ANOCA).Methods:The study data were derived from the ANOCA-CMD prospective cohort study.All enrolled patients underwent coronary angiography and concurrent coronary physiological assessments in the left anterior descending artery using pressure-wire and thermodilution techniques to obtain coronary flow reserve(CFR)and the index of microcirculatory resistance(IMR).Based on the results,CMD was classified into four subtypes:CMD with elevated IMR(IMR≥25),CMD with reduced CFR(CFR<2.5),CMD with either reduced CFR or elevated IMR(CFR<2.5 or IMR≥25),and CMD with both reduced CFR and elevated IMR(CFR<2.5 and IMR≥25).The corrected thrombolysis in myocardial infarction(TIMI)frame count(CTFC)in the left anterior descending artery was calculated from coronary angiography images,with CSF defined as CTFC>27.This study evaluated the correlation between CTFC,CFR,and IMR,and investigated the diagnostic value of CSF for CMD in ANOCA patients.Results:A total of 103 ANOCA patients were enrolled in this study,with a mean age of(64.2±10.6)years,and 53.4％were female.Among them,57 patients(55.3％)were diagnosed with coronary slow flow.Patients with slow flow had higher IMR(P<0.001)and CFR(P=0.041).Similarly,the proportion of CMD with elevated IMR was higher in the slow flow group(P<0.001),while the proportion of CMD with reduced CFR was lower(P=0.044).There was no significant difference between the groups in the proportions of CMD with either reduced CFR or elevated IMR or CMD with both reduced CFR and elevated IMR(all P>0.05).CTFC was positively correlated with hyperemic mean transit time(r=0.424,P<0.001),IMR(r=0.430,P<0.001),and CFR(r=0.211,P=0.032).The area under the curve(AUC)of CTFC for diagnosing CMD with elevated IMR was 0.721(95％CI:0.623-0.819)with an accuracy of 67％(57％,76％),for diagnosing CMD with reduced CFR was 0.610(95％CI:0.499-0.720)with an accuracy of 60％(50％,70％),for diagnosing CMD with either reduced CFR or elevated IMR was 0.549(95％CI:0.425-0.673)with an accuracy of 47％(37％,57％),and for diagnosing CMD with both reduced CFR and elevated IMR was 0.582(95％CI:0.471-0.693)with an accuracy of 47％(37％,57％).Thus,CSF demonstrated limited diagnostic values across all subtypes of CMD.Conclusions:In ANOCA patients,CSF cannot serve as an effective diagnostic marker for CMD.Therefore,in clinical practice,the slow flow phenomenon should not be directly equated with the presence of coronary microvascular dysfunction in ANOCA patients.

Objective:Investigate the impact of calcification on the long-term outcomes of patients with coronary chronic total occlusion (CTO) after percutaneous coronary intervention (PCI).Methods:A retrospective cohort study was conducted. Patients who underwent PCI and had at least one CTO lesion at Fuwai Hospital between January 2010 and December 2013 were consecutively enrolled. Calcification was evaluated by coronary angiography, and patients were divided into two groups: moderate/severe calcification group and non/mild calcification group. Clinical follow-up was completed up to 5 years. Incidence of PCI-related complications and immediate procedural outcomes were compared between two groups, and the primary endpoint was the target lesion failure (TLF) at 5 years after PCI. Clinical follow-up endpoint events were analyzed using Kaplan-Meier survival analysis with log-rank test, and Cox multivariate regression model was used to evaluate the relationship between calcification and TLF.Results:The study included 2 659 CTO patients with an age of (57.2±10.5) years, of whom 442 (16.6%) were female, and among whom 13.5% (360/2 659) had moderate/severe calcification. Compared with the non/mild calcification group, the moderate/severe calcification group had a higher incidence of PCI-related complications (43.2% (156/361) vs. 32.5% (772/2 374), P<0.001) and procedural failure (34.3% (124/361) vs. 24.3% (577/2 374), P<0.001). Additionally, the moderate/severe calcification group showed a higher risk of the primary endpoint event (TLF) during the 5-year follow-up (19.8% vs. 15.3%, log-rank P=0.028). Higher incidence of cardiac death was observed in moderate/severe calcification group (5.7% vs. 2.7%, log-rank P=0.003). Cox multivariate regression analysis revealed that moderate/severe calcified plaques remained an independent risk factor for 5-year TLF after CTO-PCI ( HR=1.34, 95% CI: 1.01-1.79, P=0.043). Conclusion:Compared with CTO patients with non/mild calcification, those with moderate/severe calcification have higher procedural failure and complication rates, as well as poorer long-term prognosis, mainly due to an increase in cardiac death.

Objectives:To investigate the impacts of American College of Cardiology/American Heart Association (ACC/AHA) coronary artery classification on the progression of coronary non-target lesions and revascularization in patients with coronary heart disease.Methods:From January 2010 to September 2014,1255 patients who underwent two consecutive coronary angiographies at Fuwai Hospital and had coronary non-target lesions were retrospectively analyzed.Lesion characteristics of all coronary non-target lesions were recorded at both procedures.All non-target lesions were divided into A,B1,B2 and C lesion group according to ACC/AHA coronary artery classification.Patients were divided into non-B2/C lesion group (noncomplex lesion group) and B2/C lesion group (complex lesion group) according to whether the non-target lesion had B2/C lesion The characteristics of all non-target coronary artery lesions and quantitative coronary angiography results were recorded.Lesion progression and revascularization were compared between different groups.Results:There were 1003 (79.9％) male patients,mean age was (58.0±9.7) years old,and 853 patients had B2/C lesions.There were 1670 non-target lesions,including 619 A/B1 lesions (214 A lesions and 405 B1 lesions) and 1051 B2/C lesions (796 B2 lesions and 255 C lesions).Follow-up time was (14.8±4.5) months.Compared with the patients in noncomplex lesion group,patients in complex lesion group were older,had lower proportion of family history of coronary heart disease and stroke (all P<0.05).The baseline levels of leukocytes,C-reactive protein,erythrocyte sedimentation rate (ESR),triglyceride and HbA1c were higher in complex lesion group than those in noncomplex lesion group.Complex lesion group had higher risk of lesion progression (21.8％ vs.13.2％,P<0.001) compared with noncomplex lesion group,similar results were observed in revascularization (16.5％ vs.11.2％,P=0.013),and there was no statistically difference in non-target lesion related myocardial infarction (P>0.05).At the lesion level,compared with A/B1 lesion,B2/C lesion was associated with a higher rate of lesion progression (17.4％ vs.11.0％,P<0.001),and a higher rate of revascularization (13.0％ vs.9.2％,P=0.018).Multivariate Cox regression analysis showed that lesion classification (B2/C) was an independent risk factor for non-target lesion progression (HR=1.732,95％CI:1.275-2.351,P<0.001) and non-target lesion revascularization (HR=1.477,95％CI:1.053-2.070,P=0.024).Conclusions:The risk of non-target lesion progression and revascularization is higher in complex groups compared with noncomplex groups according to ACC/AHA classification.So patients with complex lesions should receive more strict medical care to control related risk factors and improve their outcome.

Objectives:To investigate the impacts of American College of Cardiology/American Heart Association (ACC/AHA) coronary artery classification on the progression of coronary non-target lesions and revascularization in patients with coronary heart disease.Methods:From January 2010 to September 2014,1255 patients who underwent two consecutive coronary angiographies at Fuwai Hospital and had coronary non-target lesions were retrospectively analyzed.Lesion characteristics of all coronary non-target lesions were recorded at both procedures.All non-target lesions were divided into A,B1,B2 and C lesion group according to ACC/AHA coronary artery classification.Patients were divided into non-B2/C lesion group (noncomplex lesion group) and B2/C lesion group (complex lesion group) according to whether the non-target lesion had B2/C lesion The characteristics of all non-target coronary artery lesions and quantitative coronary angiography results were recorded.Lesion progression and revascularization were compared between different groups.Results:There were 1003 (79.9％) male patients,mean age was (58.0±9.7) years old,and 853 patients had B2/C lesions.There were 1670 non-target lesions,including 619 A/B1 lesions (214 A lesions and 405 B1 lesions) and 1051 B2/C lesions (796 B2 lesions and 255 C lesions).Follow-up time was (14.8±4.5) months.Compared with the patients in noncomplex lesion group,patients in complex lesion group were older,had lower proportion of family history of coronary heart disease and stroke (all P<0.05).The baseline levels of leukocytes,C-reactive protein,erythrocyte sedimentation rate (ESR),triglyceride and HbA1c were higher in complex lesion group than those in noncomplex lesion group.Complex lesion group had higher risk of lesion progression (21.8％ vs.13.2％,P<0.001) compared with noncomplex lesion group,similar results were observed in revascularization (16.5％ vs.11.2％,P=0.013),and there was no statistically difference in non-target lesion related myocardial infarction (P>0.05).At the lesion level,compared with A/B1 lesion,B2/C lesion was associated with a higher rate of lesion progression (17.4％ vs.11.0％,P<0.001),and a higher rate of revascularization (13.0％ vs.9.2％,P=0.018).Multivariate Cox regression analysis showed that lesion classification (B2/C) was an independent risk factor for non-target lesion progression (HR=1.732,95％CI:1.275-2.351,P<0.001) and non-target lesion revascularization (HR=1.477,95％CI:1.053-2.070,P=0.024).Conclusions:The risk of non-target lesion progression and revascularization is higher in complex groups compared with noncomplex groups according to ACC/AHA classification.So patients with complex lesions should receive more strict medical care to control related risk factors and improve their outcome.

Objective:To explore the role and mechanism of nuclear receptor subfamily 4 group A member 1 ( NR4A1) in suppressing cisplatin nephrotoxicity. Methods:The expression of NR4A1 gene in renal cell subpopulations was analyzed using the "Tabula-muris" single cell transcriptome sequencing database. NR4A1 gene was over-expressed by lentivirus infection in HK-2 cell line and primary renal proximal tubular epithelial cells. Cell counting kit-8 was used to detect the cytotoxicity of cisplatin. The cell death ratio was analyzed using propidium iodide (PI) staining by flow cytometry. The expression of NR4A1 and nuclear factor erythroid 2-related factor 2 ( NRF2) was detected by real-time fluorescent quantitative PCR and Western blotting. Ferroptosis was analyzed by detecting the contents of malondialdehyde (MDA), oxidized glutathione (GSSG) and lipid reactive oxygen species (ROS). Results:The single cell transcriptome sequencing database showed that NR4A1 gene was the lowest expression in renal proximal tubular epithelial cell subsets. Cisplatin (50 μmol/L or 100 μmol/L) could significantly induce MDA, GSSG and lipid ROS production in renal proximal tubular epithelial cells (all P<0.01), and higher cisplatin concentration accompanied with a more increase of MDA, GSSG and lipid ROS. Compared with the control HK-2 cells, the lipid ROS content and iron ion content of HK-2 cells over-expressing NR4A1 were significantly lower (all P<0.01), and the over-expression of NR4A1 inhibited cisplatin-induced cytotoxicity and ferroptosis in renal proximal tubular epithelial cells. Mechanistically, NR4A1 up-regulated the expression of anti-ferroptosis gene NRF2 in proximal renal tubular epithelial cells ( P<0.01). Furthermore, single cell data analysis showed that, similar to the expression of NR4A1 in renal tissue subsets, NRF2 was also the lowest in renal proximal tubular epithelial cells. Conclusions:Cisplatin can induce ferroptosis of renal proximal tubular epithelial cells in a dose-dependent manner. NR4A1 can inhibit cisplatin-induced ferroptosis by up-regulating NRF2 in renal proximal tubular epithelial cells, thereby alleviating the cytotoxicity of cisplatin.

Objective To explore the anti-inflammatory and analgesic mechanism of Yinlian Tongfeng granules by network pharmacology. Methods Three main active components of Yinlian Tongfeng granules were collected from TCMSP database to predict its effective targets. Based on the network information of active components and targets, the anti-inflammatory and analgesic related targets were established by using protein-protein interaction information. The enrichment analysis of KEGG biological pathway and go function enrichment were carried out to construct the active component-target-signal pathway network and explain the main mechanism of anti-inflammatory and analgesic. Results 37 targets were closely related to anti-inflammation and analgesic effects of Yinlian Tongfeng granules, mainly on Prostaglandin endoperoxide synthase 2(PTGS2), interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factors (TNF). The mechanism of action may relate to the regulation of nuclear transcription factor B signaling pathway(NF-κB). Conclusion The study predicted the anti-inflammatory and analgesic mechanism of Yinlian Tongfeng granules, and provided theoretical basis for further verification and interpretation of its mechanism.

Objective:To comprehensively analyze the medical resources and services supply in the cancer field of China.Methods:Data of 2018 were sampled from 41 tertiary public cancer hospitals in China, and the factor analysis method was used to extract common factors in resources or services, scoring respectively. Pearson correlation analysis was used in the collinearity test of the variables of both groups of common factors, while the second-order clustering method was used to analyze characteristic differences between the hospitals, and category difference was compared with t test. Results:Resource evaluation covered the two dimensions of basic resources(medical service and basic assurance resources)and high-end resources(high-end talents and academic resources). Service evaluation covered the two dimensions of medical service assurance(clinical services and basic assurance)and disciplinary sphere of influence(discipline construction and clinical efficiency). The factor of basic manpower and beds was significantly correlated with that of medical service and basic assurance( r=0.811, P<0.001), while the factor of high-end talents and academic resources was significantly correlated with that disciplinary construction and resource efficiency( r=0.906, P<0.001). The second-order cluster analysis found the 41 cancer hospitals as two categories, with the first category of five in Guangdong, Shanghai, Beijing and Tianjin, and the second category of the rest 36 hospitals. Significant differences were found between the two categories in terms of resource scoring, service scoring, high-end resources and disciplinary sphere of influence( P<0.001). Meanwhile, the GDP per capita of the cities in which these hospitals are located also had significant differences( P<0.001). Conclusions:Development of public tertiary cancer hospitals in China was imbalanced, as their differences were mainly found in levels of disciplinary development and efficiency of clinical services, which were closely related to the high-end talents and academic resources of the hospital in question.Furthermore, high quality medical care was mostly located in regions of higher development. The authors recommend to take a balanced consideration of the differences and distribution of cancer care services in China, in terms of performance classification of public hospitals and establishment of regional cancer centers of the country.

Objective To investigate the anti-inflammatory and analgesic effects of the active fractions of Tongfeng granules on rats with arthritis induced by complete Freund's adjuvant. Methods 56 SD rats were randomly divided into seven groups, blank group, model group, total flavonoids group, total organic acid group, total alkaloid group, Tongfeng granule group and positive control group. Except for the blank group, the remaining 6 groups established joints pathological model of inflammation. 15 days after the successful modeling, intragastric drug administration was continued for 30 days. The swelling of ankle joint, WBC, N%, IL-6, IL-10, TNF-α and the histopathology of joint were measured. Results Comparing with the model group, each effective fraction group of Tongfeng granules, Gout granules and positive control group decreased the ankle joint swelling rate significantly (P<0.01) and reduced fibrous tissue proliferation. There was no significant difference in WBC and N% of neutrophils. They significantly reduce the level of serum IL-6 and TNF-α, and increase the level of IL-10 (P<0.05, P<0.01). Conclusion This study clarifies the anti-inflammatory and analgesic effects of active fractions of Tongfeng granules and provides a basis for further clinical medication and preparation development.