Uneven primary healthcare supply of rural doctors and medical equipment in remote China: community impact and the moderating effect of policy intervention.

BACKGROUND: Unequal access to primary healthcare (PHC) has become a critical issue in global health inequalities, requiring governments to implement policies tailored to communities' needs and abilities. However, the place-based facility dimension of PHCs is oversimplified in current healthcare literature, and formulating the equity-oriented PHC spatial planning remains challenging without understanding the multiple impacts of community socio-spatial dynamics, particularly in remote areas. This study aims to push the boundary of PHC studies one step further by presenting a nuanced and dynamic understanding of the impact of community environments on the uneven primary healthcare supply. METHODS: Focusing on Shuicheng, a remote rural area in southwestern China, multiple data are included in this village-based study, i.e., the facility-level healthcare statistics data (2016-2019), the statistical yearbooks, WorldPop, and Chinese GDP's spatial distribution data. We evaluate villages' PHC service capacity using the number of doctors and essential equipment per capita, which are the major components of China's PHC delivery. The indicators describing community environments are selected based on extant literature and China's planning paradigms, including town- and village-level factors. Gini coefficients and local spatial autocorrelation analysis are used to present the divergences of PHC capacity, and multilevel regression model and (heterogeneous) difference in difference model are used to examine the driving role of community environments and the dynamics under the policy intervention. RESULTS: Despite the general improvement, PHC inequalities remain significant in remote rural areas. The village's location, aging, topography, ethnic autonomy, and economic conditions significantly influence village-level PHC capacity, while demographic characteristics and healthcare delivery at the town level are also important. Although it may improve the hardware setting in village clinics (coef. = 0.350), the recent equity-oriented policy attempts may accelerate the loss of rural doctors (coef. = - 0.517). Notably, the associations between PHC and community environments are affected inconsistently by this round of policy intervention. The town healthcare centers with higher inpatient service capacity (coef. = - 0.514) and more licensed doctors (coef. = - 0.587) and nurses (coef. = - 0.344) may indicate more detrimental policy effects that reduced the number of rural doctors, while the centers with more professional equipment (coef. = 0.504) and nurses (coef. = 0.184) are beneficial for the improvement of hardware setting in clinics. CONCLUSIONS: The findings suggest that the PHC inequalities are increasingly a result of joint social, economic, and institutional forces in recent years, underlining the increased complexity of the PHC resource allocation mechanism. Therefore, we claim the necessity to incorporate a broader understanding of community orientation in PHC delivery, particularly the interdisciplinary knowledge of the spatial lens of community, to support its sustainable development. Our findings also provide timely policy insights for ongoing primary healthcare reform in China.

Free triiodothyronine to free thyroxine ratio as a marker of poor prognosis in euthyroid patients with acute coronary syndrome and diabetes after percutaneous coronary intervention.

Objectives: In recent years, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, a new comprehensive index for evaluating thyroid function, which could reflect thyroid function more stably and truly than serum thyroid hormone level, has been demonstrated to correlate with the risks of diabetes and cardiovascular disease in euthyroid adults. However, the correlation between thyroid hormone sensitivity and long-term prognosis in euthyroid patients with acute coronary syndrome (ACS) and diabetes after percutaneous coronary intervention (PCI) remains unclear. Methods: A total of 1,786 euthyroid patients with ACS who successfully underwent PCI at Beijing Anzhen Hospital from August 2021 to April 2022 were included in our study, which was divided into three groups according to tertiles of thyroid hormone sensitivity index. Cox regression, Kaplan-Meier, and receiver operating characteristic analyses were applied to analyze the associations between the FT3/FT4 ratio with ACS and diabetes after PCI. Results: Our analysis indicated that a lower level of FT3/FT4 ratio in euthyroid patients with acute coronary syndrome (ACS) and diabetes after PCI showed significantly higher incidences of major adverse cardiac and cerebrovascular events (MACCE) when compared with a higher level of FT3/FT4 ratio. After adjusting for other covariates, patients with a lower level of FT3/FT4 ratio were negatively associated with the risk of MACCE than those with a higher level of FT3/FT4 ratio (adjusted OR =1.61, 95% CI 1.05-2.47, P = 0.028). In subgroup analyses, individuals were stratified by age, sex, BMI, ACS type, hypertension, and dyslipidemia, showing that there were no significant interactions between the FT3/FT4 ratio and all subgroups for MACCE. In addition, the FT3/FT4 ratio performed better on ROC analyses for cardiac death prediction [area under the curve (AUC), 0.738]. Conclusion: A reduced level of FT3/FT4 ratio was a potential marker of poor prognosis in euthyroid patients with ACS and diabetes after PCI.

Estimated pulse wave velocity and cognitive outcomes: A post hoc analysis of SPRINT-MIND.

BACKGROUND: Arterial stiffness has been confirmed to be associated with cognitive impairment. Carotid-femoral pulse wave velocity (cfPWV) is widely regarded as the gold standard for assessing arterial stiffness, yet it is not readily accessible. In response, the use of estimated pulse wave velocity (ePWV) has been proposed as a more accessible and cost-effective alternative. ePWV not only offers ease of calculation but also covers a broader spectrum of vascular aging processes, some of which may be distinct from those detected by cfPWV. The aim of our study was to investigate the association between ePWV and cognitive outcomes in SPRINT-MIND (Systolic Blood Pressure Intervention Trial Memory and Cognition in Decreased Hypertension). METHODS: This study was a post-hoc analysis of the SPRINT-MIND. The primary endpoint was a composite outcome including probable dementia and mild cognitive impairment (MCI). The calculation of ePWV was based on age and mean blood pressure. The association between ePWV and cognitive outcomes was assessed using Cox regression analysis. The response of ePWV to antihypertensive treatment at 12 months was used to define treatment efficacy. RESULTS: 8563 patients were enrolled. The ePWV was found to be independently associated with risk of probable dementia (Tertile 3 vs. Tertile 1: HR, 95% CI: 1.70, 1.08-2.68, P = 0.023, P for trend = 0.013), MCI (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.35, 1.71-3.23, P < 0.001, P for trend < 0.001), and the composite outcome of probable dementia or MCI (Tertile 3 vs. Tertile 1: HR, 95% CI: 2.17, 1.65-2.86, P < 0.001, P for trend < 0.001). The combined effect of treatment allocation and the response of ePWV to treatment exhibited that intensive/ePWV responders had the lowest risk of the primary outcome (Log-rank P = 0.002). CONCLUSION: EPWV demonstrated independent predictive value for cognitive outcomes in SPRINT-MIND.

Combination of the glycated hemoglobin levels and prognostic nutritional index as a prognostic marker in patients with acute coronary syndrome and type 2 diabetes mellitus.

BACKGROUND: Increased susceptibility to malnutrition and inadequate glycemic control are frequently observed in diabetic patients with coronary artery disease. The assessment of malnutrition is performed using the prognosis nutritional index (PNI). The inadequate glycemic control is measured using glycated hemoglobin (HbA1c). However, the combined effect of PNI and HbA1c on the prognosis in diabetic patients with coronary artery disease remains unknown. METHODS: A study was conducted at Beijing Anzhen Hospital and included 2,005 patients diagnosed with type 2 diabetes mellitus (T2DM) accompanied by acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) from September 2021 to January 2022. Based on the median PNI and HbA1c, we categorized the patients into four groups including high (H)-PNI/low (L)-HbA1c, H-PNI/H-HbA1c, L-PNI/L-HbA1c, and L-PNI/H-HbA1c. Major adverse cardiac and cerebrovascular events (MACCE) were the primary outcome, including all-cause mortality, nonfatal myocardial infarction (MI), and nonfatal strokes. RESULTS: Throughout a median follow-up of 16.3 months, 73 patients had MACCE, which comprised 36 cases of all-cause mortality. In comparison to the H-PNI, the L-PNI showed an obvious rise in MACCE and all-cause mortality (log-rank P = 0.048 and 0.021, respectively) among the H-HbA1c group. Compared to the other groups, the L-PNI/H-HbA1c group exhibited the greatest risk of MACCE (adjusted hazard ratio [aHR]: 2.50, 95% confidence interval [CI] 1.20-5.23, P = 0.014) and all-cause mortality (HR: 3.20, 95% CI 1.04-9.82, P = 0.042). With the addition of PNI, MACCE and all-cause mortality prediction models performed significantly better in patients with ACS and T2DM after PCI, particularly in those with H-HbA1c levels. CONCLUSIONS: The combination of L-PNI and H-HbA1c is a prognostic marker for MACCE and all-cause mortality in patients diagnosed with ACS and T2DM who underwent PCI. The PNI can serve as an assessment tool of malnutrition in patients with ACS and T2DM accompanied by H-HbA1c who underwent PCI. Therefore, monitoring the long-term change of the PNI deserves attention in clinical practice.

Association between the cumulative average triglyceride glucose-body mass index and cardiovascular disease incidence among the middle-aged and older population: a prospective nationwide cohort study in China.

BACKGROUND: Findings from earlier research have established that insulin resistance (IR) is implicated in atherosclerosis progression, representing a noteworthy risk factor for cardiovascular disease (CVD). Recently, the triglyceride glucose-body mass index (TyG-BMI) has been introduced as a straightforward and robust alternative indicator for early detection of IR. Nevertheless, there is a scarcity of studies that have examined the capability of TyG-BMI for predicting incident CVD. Consequently, the core objective of this study was to determine whether the cumulative average TyG-BMI correlated with CVD incidence. METHODS: All data was sourced from the China Health and Retirement Longitudinal Study (CHARLS). The exposure was the cumulative average TyG-BMI, determined by the average of TyG-BMI values for the baseline and follow-up investigations (Wave 1 in 2011, Wave 3 in 2015, respectively). The calculation of TyG-BMI involved a combination of triglyceride, fasting blood glucose, and body mass index. The primary outcome was incident CVD. Logistic regression analyses as well as restricted cubic spline (RCS) regression analyses were performed for examining the association between the cumulative average TyG-BMI and CVD incidence. RESULTS: In all, 5,418 participants were enrolled in our analysis, with 2,904 (53.6%) being female, and a mean (standard deviation, SD) age of 59.6 (8.8) years. The mean (SD) cumulative average TyG-BMI among all participants was 204.9 (35.7). Totally, during a 4-year follow-up, 543 (10.0%) participants developed CVD. The fully adjusted logistic regression analysis revealed a significant association between the cumulative average TyG-BMI and incident CVD [odds ratio (OR), 95% confidence interval (CI): 1.168, 1.040-1.310, per 1 SD increase]. The RCS regression analysis displayed a positive, linear association of the cumulative average TyG-BMI with CVD incidence (P for overall = 0.038, P for nonlinear = 0.436). CONCLUSIONS: Our study revealed a noteworthy correlation between the cumulative average TyG-BMI and incident CVD among the middle-aged and older population. The cumulative average TyG-BMI emerges as a valuable tool that may enhance the primary prevention and treatment of CVD.

Platelet to albumin ratio: A risk factor related to prognosis in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: Atherosclerotic cardiovascular disease (ASCAD) is recognized as a chronic subclinical systemic inflammatory condition. The platelet-albumin ratio (PAR) has shown promise in prognosticating various inflammation-related disorders. Our study aimed to assess the connection between PAR and major adverse cardiovascular events (MACE) in percutaneous coronary intervention (PCI)-treated patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). METHODS: PAR, derived from platelet and albumin counts, categorized participants into four quartiles. The primary outcome was composite MACE, encompassing all-cause mortality, non-fatal myocardial infarction (MI), and ischemia-driven revascularization. Secondary outcomes comprised individual MACE components. Multivariate Cox regression evaluated PAR's independent impact on adverse events. The non-linear relationship between the PAR value and MACE was explored using a restricted cubic spline (RCS). Receiver operating characteristic (ROC) analysis was conducted and the area under the curve (AUC) was calculated. Subgroup analysis was used to determine the effect of PAR on MACE in different subgroups. RESULTS: Enrolling 1391 NSTE-ACS patients, high PAR quartiles were correlated with elevated MACE rates (quartile 4 vs. quartile 1: 33.5% vs. 10.2%, p < 0.001). PAR was revealed to be independently related to an increased risk of MACE (quartile 4 vs. quartile 1: HR, 2.04 [95% CI, 1.34-3.08], p = 0.001). RCS indicated a positive PAR-MACE relationship. The AUC of PAR for the 3-year MACE was 0.659 (95% CI: 0.626-0.677, P<0.001). Subgroup analysis showed no significant interactions across subsets. CONCLUSION: PAR independently predicted MACE risk in PCI-treated NSTE-ACS patients.

hIMB1636-MMAE, a Novel TROP2-Targeting Antibody-Drug Conjugate Exerting Potent Antitumor Efficacy in Pancreatic Cancer.

Herein, we first prepared a novel anti-TROP2 antibody-drug conjugate (ADC) hIMB1636-MMAE using hIMB1636 antibody chemically coupled to monomethyl auristatin E (MMAE) via a Valine-Citrulline linker and then reported its characteristics and antitumor activity. With a DAR of 3.92, it binds specifically to both recombinant antigen (KD ∼ 0.687 nM) and cancer cells and could be internalized by target cells and selectively kill them with IC50 values at nanomolar/subnanomolar levels by inducing apoptosis and G2/M phase arrest. hIMB1636-MMAE also inhibited cell migration, induced ADCC effects, and had bystander effects. It displayed significant tumor-targeting ability and excellent tumor-suppressive effects in vivo, resulting in 5/8 tumor elimination at 12 mg/kg in the T3M4 xenograft model or complete tumor disappearance at 10 mg/kg in BxPc-3 xenografts in nude mice. Its half-life in mice was about 87 h. These data suggested that hIMB1636-MMAE was a promising candidate for the treatment of pancreatic cancer with TROP2 overexpression.

Slow magnetic relaxation in 8-coordinate Mn(II) compounds.

The design and synthesis of high-spin Mn(II)-based single-molecule magnets (SMMs) have not been well developed to a great extent, as compared with a large number of SMMs based on the other first row transition metal complexes. In light of our success in designing Fe(II), Co(II) and Fe(III)-based SMMs with a high coordination number of 8, it is of great interest to design Mn(II) analogues with such a strategy. In this contribution, four Mn(II) compounds, [MnII(Ln)2](ClO4)2 (1-4) were obtained from reactions of neutral tetradentate ligands, L1-L4, with hydrated MnII(ClO4)2 (L1 = 2,9-bis(carbomethoxy)-1,10-phenanthroline, L2 = 2,9-bis(carbomethoxy)-2,2'-dipyridine, L3 = N2,N9-dibutyl-1,10-phenanthroline-2,9-dicarboxamide, L4 = 6,6'-bis(2-(tert-butyl)-2H-tetrazol-5-yl)-2,2'-bipyridine). Their crystal structures have been determined by X-ray crystallography and it clearly shows that the Mn(II) centers in these compounds have an oversaturated coordination number of 8. Their magnetic properties have been investigated in detail; to our surprise, all of these Mn(II) compounds show interesting slow magnetic relaxation behaviors under an applied direct current field, although they have very small negative D values.

Long-term safety of ultrathin bioabsorbable-polymer sirolimus-eluting stents versus thin durable-polymer drug-eluting stents in acute coronary syndrome: A systematic review and meta-analysis.

BACKGROUND: Because of the advancement of bioabsorbable polymers and thinner struts, bioabsorbable-polymer sirolimus-eluting stents (BP-SES) with ultrathin struts may be related to superior performance when compared to durable-polymer drug-eluting stents (DP-DES) with thin struts. Nonetheless, the long-term safety of ultrathin BP-SES in acute coronary syndrome (ACS) remains unknown. METHODS: We sought to assess the long-term safety of ultrathin BP-SES in ACS patients, conducting a thorough meta-analysis of all relevant trials drawing a comparison between ultrathin BP-SES and contemporary thin DP-DES. Target lesion failure (TLF), which includes cardiac death (CD), target-vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (CD-TLR) was considered the primary endpoint. Multiple databases comprising Embase, MEDLINE, Cochrane Library, and Pubmed were all thoroughly searched. RESULTS: There were seven randomized controlled trials included in our study with 7522 randomized patients with ACS (BP-SES = 3888, DP-DES = 3634). TLF occurred in 371 (9.5% in BP-SES) and 393 (10.8% in DP-DES) patients, respectively, across a 40.7-month weighted mean follow-up, with no statistically significant group differences (risk ratio [RR]: 0.87; 95% confidence interval [CI]: 0.73-1.04; p = .12). Furthermore, no significant differences in cardiac death (RR: 0.96; 95% CI: 0.68-1.35; p = .81), TV-MI (RR: 0.63; 95% CI: 0.36-1.10; p = .10) and CD-TLR (RR: 0.77; 95% CI: 0.46-1.29; p = .32) were detected between two groups. CONCLUSION: During a follow-up of 40.7 months, ultrathin BP-SES and thin DP-DES had a comparable risk of TLF and its individual components (CD, TV-MI, and CD-TLR), indicating that ultrathin BP-SES held at least the same safety and efficiency as thin DP-DES presented in patients with ACS.

Effect of diabetes mellitus on young female patients with acute coronary syndrome.

BACKGROUND: Diabetes mellitus (DM) is one of the most important risk factors of acute coronary syndrome (ACS). There have been many studies on the relationship between DM and ACS. However, the effect of DM on young females with ACS is still unclear. OBJECTIVE: To explore the effect of DM on coronary arteries lesions in young females with ACS. METHODS: 1278 young females (age ≤ 44 years) undergoing coronary angiography were divided into DM group (n = 197) and control group (n = 1081) according to whether they had diabetes. Based on whether the patient has ACS, each group was further divided into DM-ACS subgroup and Non-DM-ACS subgroup to compare the characteristics and severity of coronary artery lesions and follow-up outcomes. RESULTS: The prevalence of diabetes was 15.41% (197/1278). Overweight (58.88%) and depression or anxiety (11.17%) in the DM group was significantly higher than those (32.22% and 6.20%) in the control group (P < 0.05). The prevalence of ACS (85.28%) in the DM group was significantly higher than that (25.35%) in the control group (P < 0.05). The proportion of type A lesions in the DM-ACS subgroup was lesser than that in the Non-DM-ACS subgroup (P < 0.05). The type C lesions in the DM-ACS subgroup were significantly higher than that in the Non-DM-ACS subgroup (P < 0.01). The number of stents implantation in the DM-ACS subgroup was no significant difference compared with the Non-DM-subgroup (P > 0.05). The length of stent implantation in the DM-ACS subgroup was significantly longer than that in the Non-DM-ACS subgroup (P < 0.05). The rate of MACE was not statistically significant between the two subgroups (P > 0.05), but the rate of all-cause death (2.98%) in the DM-ACS subgroup was significantly higher than that (0.36%) in the Non-DM-ACS subgroup (P < 0.05). CONCLUSIONS: DM is an important risk factor in young females with ACS. Young women with diabetes are prone to coronary heart disease. The coronary artery lesions in DM patients were more severe than those in Non-DM patients, despite the protective effect of estrogen on the cardiovascular system. Therefore, young women with DM should be treated to prevent ACS and future events activelyandpurposefully.

The predictive value of atherogenic index of plasma for cardiovascular outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention with LDL-C below 1.8mmol/L.

BACKGROUND: The potential predictive significance of atherogenic index of plasma (AIP) for cardiovascular outcomes in patients with acute coronary syndrome (ACS) and who have undergone percutaneous coronary intervention (PCI), with low-density lipoprotein-cholesterol (LDL-C) below 1.8mmol/L, has not been well explored. METHODS: The retrospective cohort analysis included 1,133 patients with ACS and LDL-C levels below 1.8mmol/L who underwent PCI. AIP is calculated as log (triglyceride/high-density lipoprotein-cholesterol). Patients were divided into two groups according to the median value of AIP. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause death, nonfatal myocardial infarction, ischemic stroke or unplanned repeat revascularization. The association between AIP and the prevalence of MACCE was evaluated using multivariable Cox proportional hazard models. RESULTS: Over a median follow-up of 26 months, the incidence of MACCE was higher in the high AIP group compared to the low AIP group (9.6% vs. 6.0%, P log-rank = 0.020), and the difference was mainly derived from an increased risk of unplanned repeat revascularization (7.6% vs. 4.6%, P log-rank = 0.028). After adjusting for multiple variables, elevated AIP was independently associated with an increased risk of MACCE, regardless of whether AIP was considered a nominal or continuous variable (hazard ratio [HR] 1.62, 95% confidence interval [CI] 1.04-2.53 or HR 2.01, 95% CI 1.09-3.73). CONCLUSIONS: The present study demonstrates that AIP is a significant predictor of adverse outcomes in ACS patients undergoing PCI with LDL-C < 1.8mmol/L. These results suggest that AIP may offer supplementary prognostic information for ACS patients with optimally managed LDL-C levels.

NOX2 inhibition stabilizes vulnerable plaques by enhancing macrophage efferocytosis via MertK/PI3K/AKT pathway.

NADPH oxidases 2 (NOX2) is the main source of ROS in macrophages, which plays a critical role in the formation of atherosclerosis. However, effects of NOX2 inhibition on established vulnerable plaques and the potential role involved remain unclear. The purpose of this study is to investigate the latent mechanism of NOX2-triggered vulnerable plaque development. We generated a vulnerable carotid plaque model induced by carotid branch ligation and renal artery constriction, combined with a high-fat diet in ApoE-/- mice. NOX2 specific inhibitor, GSK2795039 (10 mg/kg/day by intragastric administration for 8 weeks) significantly prevented vulnerable plaque, evaluated by micro-ultrasound imaging parameters. A profile of less intraplaque hemorrhage detection, increased collagen-lipid ratio, fibrous cap thickness and less necrotic core formation were also found in GSK2795039 treated group. Mechanistically, reduced 4-HNE, in situ lesional apoptosis and enhanced efferocytosis were involved in mice treated with NOX2 inhibitor. Further analysis in mouse macrophages confirmed the role of NOX2 inhibition in enhancing macrophage efferocytosis by regulating the MertK/PI3K/AKT pathway. In summary, our data defined previously few recognized roles of NOX2 in vulnerable plaque pathogenesis and an undescribed NOX2-ROS-MerTK axis acts involved in regulating macrophage efferocytosis in the formation of rupture-prone vulnerable plaques.

Circularly polarized luminescence and magneto-optic effects from chiral Dy(III) single molecule magnets.

A new pair of multifunctional Zn(II)-Dy(III) enantiomers based on the chiral Schiff-base ligands [R,R-ZnLDy(H2O)(NO3)3] (1R2R-ZnDy) and [S,S-ZnLDy(H2O)(NO3)3] (1S2S-ZnDy) (H2L = phenol, 2,2'-[[(1R,2R/1S,2S)-1,2-diphenyl-1,2-ethanediyl]bis[(E)-nitrilomethylidyne]]bis[6-methoxy]) was synthesized and characterized. Magnetic studies indicate that 1R2R-ZnDy behaves as a single-molecule magnet. Enantiomers 1R2R-ZnDy and 1S2S-ZnDy show chiroptical activity and circularly polarized luminescence in the N,N-dimethylformamide (DMF) solution. The chiral Zn(II)-Dy(III) complexes display magnetic circular dichroism signals at room temperature. Accordingly, these complexes will inspire intriguing research on single-molecule magnets with circular polarization of luminescence activity and magneto-optic effects, which will give new clues to design multifunctional molecular magnetic materials.

Long term clinical outcome after success re-attempt percutaneous coronary intervention of chronic total occlusion.

BACKGROUND: To evaluate the long-term outcome after re-attempt CTO-PCI. METHODS: This is a retrospective cohort study that included 113 re-attempt CTO-PCI patients who were consecutively registered from January 2019 to December 2020 at Beijing Anzhen Hospital's Center of Coronary Artery Disease. All patients were divided into two groups based on procedural success or failure. The primary endpoint was major adverse cardiac events (MACE), a composite of all-cause mortality, myocardial infarction and target vessel revascularization (TVR). The secondary endpoint was angina after PCI. RESULTS: Overall, the successful re-attempt CTO-PCI was archived in 77 patients, the failed CTO-PCI was performed in 36 patients. After a median follow-up of 21.7 months (interquartile range: 10.9-26.0), the incidence of the primary outcome was significantly lower in the success group [14.2% vs. 38.9%, adjusted hazard ratio (HR) 0.351, 95% CI 0.134-0.917, P = 0.033], mainly driven by the reduction of TVR (9.1% vs. 30.6%, adjusted HR 0.238, 95% CI: 0.078-0.72, P = 0.011). Furthermore, patients who had successful re-attempt CTO-PCI had a lower risk of angina after PCI (27.3% vs.61.1%, adjusted HR 0.357, 95% CI 0.167-0.76, P = 0.008). The risk factors of TVR in the patients with successful re-attempt CTO-PCI were stent length > 100 mm (adjusted HR 21.805, 95% CI 1.765-269.368, P = 0.016) and J-CTO score > 3(adjusted HR: 9.733, 95% CI:1.533-61.797, P = 0.016). CONCLUSIONS: For the patients with previous CTO-PCI failure, a successful re-attempt CTO-PCI was associated with significantly lower MACE, which was primarily driven by a lower TVR rate. More complex CTO lesions and longer stents were the independent predictors of TVR after successful CTO-PCI.

Triglyceride-glucose index level and variability and outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention: an observational cohort study.

BACKGROUND: The associations between the long-term triglyceride-glucose (TyG) index level and variability and clinical outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) have not been well studied. METHODS: A total of 1,694 ACS patients with at least three postbaseline TyG index measurements within 2 years after PCI were included in the present study. The TyG index was defined as ln (fasting triglycerides [mg/dL] × fasting plasma glucose [mg/dL]/2). Multivariable-adjusted Cox proportional hazard models were used to examine the association between baseline and mean TyG index levels and TyG index variability and the risk of major adverse cardiovascular and cerebrovascular events (MACCEs). RESULTS: During the median follow-up of 31 months, the overall incidence of MACCE was 5.9%. Both high baseline and mean TyG index levels were independently associated with an increased risk of MACCEs after adjustment for multiple potential confounders (hazard ratio [HR) 1.76 95% confidence interval [CI] 1.06-2.93; and HR 2.73 95% CI 1.57-4.74). Similarly, higher TyG index variability by successive variation (SD) was well related to a higher prevalence of MACCEs (HR 2.17 95% CI 1.28-3.68). In addition, the mean TyG index level showed a stronger risk prediction for MACCEs than the baseline TyG index level and TyG index-SD (AUCs 0.618 vs 0.566 vs 0.566). CONCLUSIONS: The risk of MACCEs significantly increased with higher baseline and mean TyG index levels, as well as TyG index variability, in patients with ACS undergoing PCI. In particular, the mean TyG index level exhibited the highest predicting ability for MACCEs. Therefore, monitoring the long-term pattern of the TyG index deserves attention in clinical practice.

Drug-resistant HER2-positive breast cancer: Molecular mechanisms and overcoming strategies.

Breast cancer is one of the most common malignancies and the leading cause of cancer-related death in women. HER2 overexpression is a factor for poor prognosis in breast cancer, and anti-HER2 therapy improves survival in these patients. A dual-targeted combination of pertuzumab and trastuzumab, alongside cytotoxic chemotherapy, constitutes the primary treatment option for individuals with early-stage, HER2-positive breast cancer. Antibody-drug conjugate (ADC) and tyrosine kinase inhibitors (TKI) also increase the prognosis for patients with metastatic breast cancer. However, resistance to targeted therapy eventually occurs. Therefore, it is critical to investigate how HER2-positive breast cancer is resistant to targeted therapy and to develop novel drugs or strategies to overcome the resistance simultaneously. This review aims to provide a comprehensive discussion of the HER2-targeted agents currently in clinical practice, the molecular mechanisms of resistance to these drugs, and the potential strategies for overcoming resistance.

The long-term clinical outcomes of intravascular ultrasound-guided versus angiography-guided coronary drug eluting stent implantation in long de novo coronary lesions: A systematic review and meta-analysis.

Background: No meta-analysis has been conducted to compare the long-term clinical outcomes of intravascular ultrasound (IVUS)-guided versus angiographic-guided drug-eluting stent implantation in patients with long de novo coronary lesions. We attempted to compare the efficacy and safety of IVUS guidance versus angiography guidance in percutaneous coronary intervention (PCI) for long de novo coronary lesions. Materials and Methods: We performed a detailed meta-analysis from four randomized controlled trials (RCTs) and one observational study to compare long outcomes of IVUS versus angiography in guiding coronary stent implantation with long de novo coronary lesions defined as coronary stenosis which need stent implantation >28 mm in length. Data were aggregated for the endpoints measure using the fixed-effects model as pooled odds ratio (OR) with 95% confidence intervals. Clinical outcomes included major adverse cardiovascular events (MACE), all revascularization, including target lesion revascularization (TLR) and target vessel revascularization (TVR), all myocardial infarction (MI), all-cause death, and stent thrombosis (ST). Cochrane Library, Embase, PubMed, and Web of Science were searched. Results: Four RCTs and one observational study were included in our study with 3,349 patients (IVUS guidance = 1,708; Angiography guidance = 1,641). With mean follow-up of 2 years, the incidence of MACE, all myocardial infarction, all revascularization and stent thrombosis were significantly lower in IVUS-guided DES implantation of patients with long de novo coronary lesions than in angiography-guided patients; MACE [OR 0.41; 95% confidence interval (CI), 0.29-0.58; p < 0.00001], all myocardial infarction (OR 0.23; 95% CI, 0.09-0.58; p = 0.002), all revascularization (OR 0.48; 95% CI, 0.36-0.66; p < 0.00001), stent thrombosis (OR 0.32; 95% CI, 0.11-0.89; p = 0.03). There was no significant difference in all-cause mortality between the two groups (OR 0.82; 95% CI, 0.55-1.23; p = 0.34). Conclusion: During mean follow-up of 2 years, the incidence of MACE, stent thrombosis, all myocardial infarction and revascularization in patients with long de novo coronary lesions under IVUS-guided PCI were significantly lower than angiography-guided PCI, and there were no statistically significant differences in all-cause mortality.

In-hospital outcomes of Ticagrelor versus Clopidogrel in high bleeding risk patients with acute coronary syndrome: Findings from the CCC-ACS project.

BACKGROUND: The optimal P2Y12 inhibitor in high bleeding risk (HBR) patients with acute coronary syndrome (ACS) remains unclear. We compared the in-hospital efficacy and safety of ticagrelor versus clopidogrel in ACS patients at HBR. METHODS: We identified 22,120 hospitalized ACS patients with HBR treated with aspirin combined with either clopidogrel (n = 17,420) or ticagrelor (n = 4700) in the Improving Care for Cardiovascular Disease in China-ACS (CCC-ACS) project between November 2014 and December 2019. RESULTS: The median length of hospital stay was 10 days (interquartile range, 7-14 days). Compared with clopidogrel, ticagrelor was associated with a higher risk of in-hospital TIMI major or minor bleeding (4.8% vs 3.8%; adjusted OR 1.20; 95% CI 1.03-1.41; P = 0.022). The incidence of TIMI major bleeding (1.7% vs 1.1%, P = 0.005) and intracranial bleeding (0.8% vs 0.5%, P = 0.005) were also higher in the ticagrelor group than in the clopidogrel group. There was no significant difference in the rate of in-hospital major adverse cardiovascular and cerebrovascular event (MACCE) (a composite of all-cause death, myocardial infarction, stent thrombosis, or ischemic stroke) with ticagrelor compared with clopidogrel therapy (4.2% vs 4.3%; adjusted OR 1.08; 95% CI 0.90-1.28; P = 0.411). Outcomes in the propensity-matched cohorts and in sensitivity analyses were consistent with the those of the main analysis. CONCLUSIONS: Among ACS patients with HBR, ticagrelor as compared with clopidogrel was associated with an increased risk of in-hospital major bleeding without a significant reduction in in-hospital MACCE. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02306616.

ENKD1 promotes CP110 removal through competing with CEP97 to initiate ciliogenesis.

Despite the importance of cilia in cell signaling and motility, the molecular mechanisms regulating cilium formation remain incompletely understood. Herein, we characterize enkurin domain-containing protein 1 (ENKD1) as a novel centrosomal protein that mediates the removal of centriolar coiled-coil protein 110 (CP110) from the mother centriole to promote ciliogenesis. We show that Enkd1 knockout mice possess ciliogenesis defects in multiple organs. Super-resolution microscopy reveals that ENKD1 is a stable component of the centrosome throughout the ciliogenesis process. Simultaneous knockdown of ENKD1 and CP110 significantly reverses the ciliogenesis defects induced by ENKD1 depletion. Protein interaction analysis shows that ENKD1 competes with centrosomal protein 97 (CEP97) in binding to CP110. Depletion of ENKD1 enhances the CP110-CEP97 interaction and detains CP110 at the mother centriole. These findings thus identify ENKD1 as a centrosomal protein and uncover a novel mechanism controlling CP110 removal from the mother centriole for the initiation of ciliogenesis.