Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ² test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 9^th to <10^th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ²=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ²=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ²=1.878, P=0.171; χ²=0.078, P=0.780; χ²=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Disturbance of macrophage-associated lipid metabolism plays a key role in atherosclerosis. Crosstalk between autophagy deficiency and inflammation response in foam cells (FCs) through epigenetic regulation is still poorly understood. Here, we demonstrate that in macrophages, oxidized low-density lipoprotein (ox-LDL) leads to abnormal crosstalk between autophagy and inflammation, thereby causing aberrant lipid metabolism mediated through a dysfunctional transcription factor EB (TFEB)-P300-bromodomain-containing protein 4 (BRD4) axis. ox-LDL led to macrophage autophagy deficiency along with TFEB cytoplasmic accumulation and increased reactive oxygen species generation. This activated P300 promoted BRD4 binding on the promoter regions of inflammatory genes, consequently contributing to inflammation with atherogenesis. Particularly, ox-LDL activated BRD4-dependent super-enhancer associated with liquid-liquid phase separation (LLPS) on the regulatory regions of inflammatory genes. Curcumin (Cur) prominently restored FCs autophagy by promoting TFEB nuclear translocation, optimizing lipid catabolism, and reducing inflammation. The consequences of P300 and BRD4 on super-enhancer formation and inflammatory response in FCs could be prevented by Cur. Furthermore, the anti-atherogenesis effect of Cur was inhibited by macrophage-specific Brd4 overexpression or Tfeb knock-out in Apoe knock-out mice via bone marrow transplantation. The findings identify a novel TFEB-P300-BRD4 axis and establish a new epigenetic paradigm by which Cur regulates autophagy, inhibits inflammation, and decreases lipid content.

BACKGROUND: The prevalence of skin diseases and diabetes mellitus (DM) are prominent around the world. The current scope of knowledge regarding the prevalence of skin diseases and comorbidities with type 2 DM (T2DM) is limited, leading to limited recognition of the correlations between skin diseases and T2DM. METHODS: We collected 383 subjects from the Da Qing Diabetes Study during the period from July 9th to September 1st, 2016. The subjects were categorized into three groups: Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. The prevalence and clinical characteristics of skin diseases were recorded and investigated. RESULTS: In this cross-sectional study, 383 individuals with ages ranging from 53 to 89-year-old were recruited. The overall prevalence of skin diseases was 93.5%, and 75.7% of individuals had two or more kinds of skin diseases. Additionally, there were 47 kinds of comorbid skin diseases in patients with T2DM, of which eight kinds of skin diseases had a prevalence >10%. The prevalence of skin diseases in NGT, IGT, and T2DM groups were 93.3%, 91.5%, and 96.6%, respectively; stratified analysis by categories showed a statistically significant difference in "disturbances of pigmentation" and "neurological and psychogenic dermatoses". The duration of T2DM also significantly associated with the prevalence of "disturbances of pigmentation" and "neurological and psychogenic dermatoses". Subsequently, the prevalence of "disturbances of pigmentation" was higher in males than females in NGT (P < 0.01) and T2DM (P < 0.01) groups. In addition, the difference in the prevalence of "disturbances of pigmentation" was also significant in NGT and T2DM groups (P < 0.01). CONCLUSIONS There was a high prevalence of skin diseases in the Da Qing Diabetes Study. To address the skin diseases in the Da Qing Diabetes Study, increased awareness and intervention measures should be implemented.
Aged ; Aged, 80 and over ; Blood Glucose ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/epidemiology* ; Female ; Glucose Intolerance/epidemiology* ; Glucose Tolerance Test ; Humans ; Male ; Middle Aged ; Skin Diseases/epidemiology*

Objective: To explore the clinical manifestations, diagnosis, treatment and prognosis of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) . Methods: A retrospective study identified 91 patients diagnosed with ALCAPA at Shanghai Children′s Medical Center from March 2010 to August 2017. According to the left ventricular ejection fraction (LVEF) at the time of consultation, patients were divided into the cardiac insufficiency group (n=54) and the normal cardiac function group (n=37). Clinical features (age of onset, clinical performance, etc) and auxiliary examinations (electrocardiogram, echocardiography, etc) between the two groups were compared using a t-test and a Chi-square test. Prognostic factors were analyzed by an ordered logistic regression and a Pearson correlation coefficient. Results: (1) The age of diagnosis of patients in the cardiac insufficiency group who were usually misdiagnosed as cardiomyopathy was (10.0±2.6) months (20/54) , whereas the age of diagnosis of patients in the normal cardiac function group who were usually misdiagnosed as valvular diseases was (40.0±7.8) months (4/37). According to the pathophysiological mechanism, forty of the 54 (74%) patients in the cardiac insufficiency group were infantile type, and 78% patients (29/37) in the normal cardiac function group were adult type. (2) Preoperative electrocardiogram showed the deep Q wave in lead I occurred more frequently in the cardiac insufficiency group than in the normal cardiac function group (28/54 vs. 11/37, χ²=4.388, P=0.036). (3) Twenty patients died in the cardiac insufficiency group including 12 patients who died from postoperative cardiac pump failure and 8 children who did not undergo surgery due to poor prognosis and died from other reasons. There was no death in the normal cardiac function group. (4) Preoperative LVEF was the unique risk factor affecting prognosis (F=16.872, P=0.005). The preoperative LVEF was significantly lower than the postoperative LVEF ((37±11)% vs. (45±14)%, t=3.614, P=0.001) in the cardiac insufficiency group. During the follow-up period, 6 patients in the cardiac insufficiency group still presented with postoperative cardiac dysfunction, and the patients in the normal cardiac function group still had normal cardiac function. Conclusions Preoperative LVEF was the unique risk factor affecting prognosis of ALCAPA. Patients with infantile type ALCAPA and preoperative cardiac insufficiency should receive long-term follow-up treatment.

Objective To explore the clinical manifestations, diagnosis, treatment and prognosis of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). Methods A retrospective study identified 91 patients diagnosed with ALCAPA at Shanghai Children′s Medical Center from March 2010 to August 2017. According to the left ventricular ejection fraction (LVEF) at the time of consultation, patients were divided into the cardiac insufficiency group (n=54) and the normal cardiac function group (n=37). Clinical features (age of onset, clinical performance, etc) and auxiliary examinations (electrocardiogram, echocardiography, etc) between the two groups were compared using a t‐test and a Chi‐square test. Prognostic factors were analyzed by an ordered logistic regression and a Pearson correlation coefficient. Results (1) The age of diagnosis of patients in the cardiac insufficiency group who were usually misdiagnosed as cardiomyopathy was (10.0±2.6) months (20/54), whereas the age of diagnosis of patients in the normal cardiac function group who were usually misdiagnosed as valvular diseases was (40.0 ± 7.8) months (4/37). According to the pathophysiological mechanism, forty of the 54 (74%) patients in the cardiac insufficiency group were infantile type, and 78% patients (29/37) in the normal cardiac function group were adult type. (2) Preoperative electrocardiogram showed the deep Q wave in lead I occurred more frequently in the cardiac insufficiency group than in the normal cardiac function group (28/54 vs. 11/37, χ2=4.388, P=0.036). (3) Twenty patients died in the cardiac insufficiency group including 12 patients who died from postoperative cardiac pump failure and 8 children who did not undergo surgery due to poor prognosis and died from other reasons. There was no death in the normal cardiac function group. (4) Preoperative LVEF was the unique risk factor affecting prognosis (F=16.872, P=0.005). The preoperative LVEF was significantly lower than the postoperative LVEF ((37±11)% vs. (45±14)%, t=3.614, P=0.001) in the cardiac insufficiency group. During the follow‐up period, 6 patients in the cardiac insufficiency group still presented with postoperative cardiac dysfunction, and the patients in the normal cardiac function group still had normal cardiac function. Conclusions Preoperative LVEF was the unique risk factor affecting prognosis of ALCAPA. Patients with infantile type ALCAPA and preoperative cardiac insufficiency should receive long‐term follow‐up treatment.

Drainage ; Humans ; Pancreas ; surgery ; Pancreaticoduodenectomy ; Stents

BACKGROUNDCoronary intervention therapy is the main treatment for uremic patients with coronary heart disease. The studies on whether dialysis reduces the efficacy of dual antiplatelet drugs are limited. The aim of this study was to examine the effect of dialysis on antiplatelet drugs in uremic patients with coronary heart disease.

METHODSThis study included 26 uremic patients who had undergone percutaneous coronary intervention in China-Japan Friendship Hospital from November 2015 to May 2017. We examined their thromboelastography results before and after hemodialysis. Self-paired t-tests were employed to analyze changes in the inhibition rate of platelet aggregation.

RESULTSThe mean inhibition rates of arachidonic acid-induced platelet aggregation before and after hemodialysis were 82.56 ± 2.79% and 86.42 ± 3.32%, respectively (t= -1.278, P= 0.213). The mean inhibition rates of adenosine diphosphate-induced platelet aggregation before and after hemodialysis were 67.87 ± 5.10% and 61.94 ± 5.90%, respectively (t = 1.425, P= 0.167). There was no significant difference in the inhibition rates of platelet aggregation before or after hemodialysis. These results also applied to patients with different sensitivity to aspirin and clopidogrel.

CONCLUSIONDialysis did not affect the antiplatelet effects of aspirin and clopidogrel in uremic patients with coronary heart disease.

Objective To investigate the hemodynamic parameters to stabilize cerebral blood flow within limits of cerebral autoregualtion. Methods We assessed the flow velocity of middle cerebral artery using transcranial Doppler and recorded invasively the blood pressure simultaneously. We then analyzed the curves of cerebral blood flow autoregulation (CBFA) and calculated upper limit of autoregulation (ULA) and lower limit of autoregulation (LLA). The values of critical closing pressue (CCP) and resistance area product (RAP) were calculated according to previous theory. The relationship between CCP, RAP and MABP were analyzed. Results In the process of increasing or decreasing blood pressure, ULA and LLA of normal rats were 148.12 ± 7.49 mmHg or 62.96 ± 3.34 mmHg, respectively. When mean artery blood pressue (MABP) changed within limits of cerebral autoregulation, the cerebral blood flow velocity changed little (increasing:0.65± 0.27 cm/s/10mmHg MABP, decreasing:0.43±0.23cm/s/10 mmHg MABP), while CCP and RAP changed significantly (in?creasing: 4.60 ± 1.06 mmHg/10mmHg MABP and 0.11 ± 0.04/10 mmHg MABP, decreasing: 6.74 ± 0.59 mmHg/10 mmHg MABP and 0.09 ± 0.02/10mmHg MABP). After fixing change of blood flow velocity, CCP and RAP were correlated with MABP more remarkablely, although all blood flow velocity, CCP and RAP were significantly correlated with MABP. Conclusion Within limits of cerebral autoregulation, stable cerebral blood flow is mainly achieved by the change of CCP and RAP against blood pressure changing on normal rats, especially the increasing or de?creasing of CCP.

Two new sulfated sesquiterpenoids, megastigman-7-ene-3, 5, 6, 9-tetrol-3-O-β-D-6'-sulfonated-glucopyranoside (1) and 3-O-β-D-6'-sulfonated-glucopyranosyl-6-(3-oxo-2-butenylidenyl)-1, 1, 5-trimethylcyclohexan-5-ol (2), along with one known sesquitepenoid compound icariside B1 (3) were isolated from the whole herb of Petasites tricholobus Franch. Their structures were identified by their chemical and spectroscopic characters. All obtained compounds were tested for their cytotoxicity against four cancer cell lines.
Cell Line, Tumor ; Glycosides ; isolation & purification ; pharmacology ; Humans ; Norisoprenoids ; isolation & purification ; pharmacology ; Petasites ; chemistry ; Sesquiterpenes ; isolation & purification ; pharmacology