Is postmastectomy radiotherapy necessary for breast cancer patients with clinically node-positive downstaging to ypN0 after neoadjuvant chemotherapy?

PURPOSE: The significance of postmastectomy radiotherapy (PMRT) in breast cancer patients who initially have clinically node-positive (cN +) status but achieve downstaging to ypN0 following neoadjuvant chemotherapy (NAC) remains uncertain. This study aims to assess the impact of PMRT in this patient subset. METHODS: Patients were enrolled from West China Hospital, Sichuan University from 2008 to 2019. Overall survival (OS), Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were estimated using the Kaplan-Meier method and assessed with the log-rank test. The impact of PMRT was further analyzed by the Cox proportional hazards model. Propensity score matching (PSM) was performed to reduce the selection bias. RESULTS: Of the 333 eligible patients, 189 (56.8%) received PMRT, and 144 (43.2%) did not. At a median follow-up period of 71 months, the five-year LRFS, DMFS, BCSS, and OS rates were 99.1%, 93.4%, 96.4%, and 94.3% for the entire cohort, respectively. Additionally, the 5-year LRFS, DMFS, BCSS, and OS rates were 98.9%, 93.8%, 96.7%, and 94.5% with PMRT and 99.2%, 91.3%, 94.9%, and 92.0% without PMRT, respectively (all p-values not statistically significant). After multivariate analysis, PMRT was not a significant risk factor for any of the endpoints. When further stratified by stage, PMRT did not show any survival benefit for patients with stage II-III diseases. CONCLUSION: In the context of comprehensive treatments, PMRT might be exempted in ypN0 breast cancer patients. Further large-scale, randomized controlled studies are required to investigate the significance of PMRT in this patient subset.

Individualized 3D-printed bolus promotes precise postmastectomy radiotherapy in patients receiving breast reconstruction.

Purpose: To evaluate the efficacy and safety of 3D-printed tissue compensations in breast cancer patients receiving breast reconstruction and postmastectomy radiotherapy (PMRT). Methods and materials: We enrolled patients with breast cancer receiving breast reconstruction and PMRT. The dose distribution of target and skin, conformability, and dose limit of organs at risk (OARs) were collected to evaluate the efficacy of the 3D-printed bolus. Radiation Therapy Oncology Group (RTOG) radiation injury classification was used to evaluated the skin toxicities. Results: A total of 30 patients diagnosed between October 2019 to July 2021 were included for analysis. Among all the patients, the 3D-printed bolus could ensure the dose coverage of planning target volume (PTV) [homogeneity index (HI) 0.12 (range: 0.08-0.18)], and the mean doses of D99%, D98%, D95%, D50%, D2% and Dmean were 4606.29cGy, 4797.04cGy, 4943.32cGy, 5216.07cGy, 5236.10cGy, 5440.28cGy and 5462.10cGy, respectively. The bolus demonstrated an excellent conformability, and the mean air gaps between the bolus and the chest wall in five quadrants were 0.04cm, 0.18cm, 0.04cm, 0.04cm and 0.07cm, respectively. In addition, the bolus had acceptable dosage limit of OARs [ipsilateral lung: Dmean 1198.68 cGy, V5 46.10%, V20 21.66%, V30 16.31%); heart: Dmean 395.40 cGy, V30 1.02%, V40 0.22%; spinal cord planning risk volume (PRV): Dmax 1634 cGy] and skin toxicity (grade 1, 76.0%; grade 2, 21.0%; grade 3, 3.3%). Conclusion: The 3D-printed bolus offers advantages in terms of dose uniformity and controllable skin toxicities in patients receiving breast reconstruction and PMRT. Further research is needed to comprehensively evaluate the effectiveness of the 3Dprinted bolus in this patient subset.

Survival and Trends in Annualized Hazard Function by Age at Diagnosis Among Chinese Breast Cancer Patients Aged ≤40 Years: Case Analysis Study.

BACKGROUND: Young breast cancer patients are more likely to develop aggressive tumor characteristics and a worse prognosis than older women, and different races and ethnicities have distinct epidemiologies and prognoses. However, few studies have evaluated the clinical biological features and relapse patterns in different age strata of young women in Asia. OBJECTIVE: We aimed to explore survival differences and the hazard function in young Chinese patients with breast cancer (BC) by age. METHODS: The patients were enrolled from West China Hospital, Sichuan University. The chi-squared test, a Kaplan-Meier analysis, a log-rank test, a Cox multivariate hazards regression model, and a hazard function were applied for data analysis. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), breast cancer-specific survival (BCSS), and overall survival (OS) were defined as end points. RESULTS: We included 1928 young BC patients diagnosed between 2008 and 2019. Patients aged 18 to 25, 26 to 30, 31 to 35, and 36 to 40 years accounted for 2.7% (n=53), 11.8% (n=228), 27.7% (n=535), and 57.7% (n=1112) of the patients, respectively. The diagnosis of young BC significantly increased from 2008 to 2019. Five-year LRFS, DMFS, BCSS, and OS for the entire population were 98.3%, 93.4%, 94.4%, and 94%, respectively. Patients aged 18 to 25 years had significantly poorer 5-year LRFS (P<.001), 5-year DMFS (P<.001), 5-year BCSS (P=.04), and 5-year OS (P=.04) than those aged 31 to 35, 26 to 30, and 36 to 40 years. The hazard curves for recurrence and metastasis for the whole cohort continuously increased over the years, while the BC mortality risk peaked at 2 to 3 years and then slowly decreased. When stratified by age, the annualized hazard function for recurrence, metastasis, and BC mortality in different age strata showed significantly different trends, especially for BC mortality. CONCLUSIONS: The annual diagnosis of young BC seemed to increase in Chinese patients, and the distinct age strata of young BC patients did not differ in survival outcome or failure pattern. Our results might provide strategies for personalized management of young BC.

Polyamines inhibit abscisic acid-induced stomatal closure by scavenging hydrogen peroxide.

Stomatal closure is regulated by plant hormones and some small molecules to reduce water loss under stress conditions. Both abscisic acid (ABA) and polyamines alone induce stomatal closure; however, whether the physiological functions of ABA and polyamines are synergistic or antagonistic with respect to inducing stomatal closure is still unknown. Here, stomatal movement in response to ABA and/or polyamines was tested in Vicia faba and Arabidopsis thaliana, and the change in the signaling components under stomatal closure was analyzed. We found that both polyamines and ABA could induce stomatal closure through similar signaling components, including the synthesis of hydrogen peroxide (H2 O2 ) and nitric oxide (NO) and the accumulation of Ca2+ . However, polyamines partially inhibited ABA-induced stomatal closure both in epidermal peels and in planta by activating antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), to eliminate the ABA-induced increase in H2 O2 . These results strongly indicate that polyamines inhibit abscisic acid-induced stomatal closure, suggesting that polyamines could be used as potential plant growth regulators to increase photosynthesis under mild drought stress.

Epstein-Barr virus DNA change level combined with tumor volume reduction ratio after inductive chemotherapy as a better prognostic predictor in locally advanced nasopharyngeal carcinoma.

BACKGROUND: To explore the prognosis predicting ability of the combined factors, Epstein-Barr virus DNA change level (EBVCL) and tumor volume reduction ratio (TVRR) after inductive chemotherapy (IC), in locally advanced nasopharyngeal carcinoma (LANPC). METHODS: From 2010 to 2018, 299 LANPC patients were included in this retrospective study. Receiver operating characteristic (ROC) curve analysis was performed to acquire the best critical values. According to the best critical values of EBVCL and TVRR, patients were stratified into low- and high-risk groups. Kaplan-Meier and ROC curve analyses were utilized to verify the prognostic ability of the new predictor (EBVCL+TVRR). The prognostic values among EBVCL+TVRR, EBVCL, TVRR, TNM stage, and the RECIST 1.1 criteria were compared by ROC curve. The primary end points were overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional failure-free survival (LRFFS). RESULTS: ROC curve analyses of TVRR on three-year survival showed the best critical values of TVRR was 32.72% for OS, 30.21% for PFS and LRFFS, 29.87% for DMFS. The best critical value of EBVCL was 127 copies/ml for OS, and 87.7 copies/ml for PFS, DMFS, and LRFFS. The three-year OS, PFS, DMFS, and LRFFS for low- and high-risk groups were 97.7% versus 78.3% (hazard ratio [HR] = 0.2398; 95% confidence interval [CI]: 0.1277-0.4502; p < 0.0001), 91.1% versus 60.9% (HR = 0.3294; 95% CI: 0.2050-0.5292; p < 0.0001), 94.2% versus 68.7% (HR = 0.2413; 95% CI: 0.1284-0.4535; p < 0.0001) and 97.8% versus 77.9% (HR = 0.3078; 95% CI: 0.1700-0.5573; p = 0.0001), respectively. The maximal area under ROC curve of EBVCL+TVRR, EBVCL, TVRR, TNM stage, and RECIST 1.1 criteria for three-year OS was 0.829, 0.750, 0.711, 0.555, and 0.605, respectively. CONCLUSION: The new-developed indicator (EBVCL+TVRR) could better predict the LANPC patient's survival after IC compared with TNM stage system or RECIST 1.1 criteria.

Effects of Buyang Huanwu Decoction on Intestinal Barrier, Intestinal Flora, and Trimethylamine Oxide in Rats with Heart Failure.

OBJECTIVE: To explore the mechanisms of Buyang Huanwu Decoction (BYHWD) modulating the gut microbiome and trimethylamine oxide (TAMO) to exert cardioprotective effects. METHODS: Ligation of the left anterior descending coronary artery was performed in rats to induce heart failure (HF). Except for the sham-operation group (n=10), 36 operation-induced models were randomized into 3 groups using a random number table (n=12 in each group): the model group, the BYHWD group (15.02 g/kg BYHWD), and the positive group (4.99 g/kg metoprolol succinate). After 4-week treatment (once daily by gavage), echocardiography was applied to evaluate the cardiac function and the Tei index (the ratio of ventricular isovolumic contraction time (IVCT) and isovolumic diastolic time (IVRT) to ejection time (ET)) was calculated; hematoxylin-eosin (HE) staining was observed to characterize the pathology of the myocardium and small intestinal villi. D-lactic acid was detected by an enzyme-linked immunosorbent assay (ELISA). Expressions of occludin, claudin-1, and zonula occludens (ZO-1) were detected by Western blot. 16S ribosomal ribonucleic acid (16S rRNA) sequencing was used to explore the changes in the intestinal flora. TMAO was detected via liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: In the echocardiography, the Tei index was considerably lower in the positive and BYHWD groups compared with the model group (P<0.05). Besides, BYHWD improved the pathology of myocardium and small intestine of HF rats and lowered the D-lactic acid content in the serum, when compared with the model group (P<0.05). BYHWD also improved the expression of occludin and claudin-1 (P<0.05); in the gut microbiota analysis, BYHWD slowed down modifications in the structure distribution of gut microbiota and regulated the diversity of intestinal flora in HF rats. The content of TMAO in the serum was significantly lowered by BYWHT compared with the model group (P<0.05). CONCLUSION: BYHWD may delay progression of HF by enhancing the intestinal barrier structure, and regulating intestinal flora and TAMO.

Promotion of Lung Cancer Metastasis by SIRT2-Mediated Extracellular Protein Deacetylation.

Acetylation of extracellular proteins has been observed in many independent studies where particular attention has been given to the dynamic change of the microenvironmental protein post-translational modifications. While extracellular proteins can be acetylated within the cells prior to their micro-environmental distribution, their deacetylation in a tumor microenvironment remains elusive. Here it is described that multiple acetyl-vWA domain-carrying proteins including integrin ß3 (ITGB3) and collagen 6A (COL6A) are deacetylated by Sirtuin family member SIRT2 in extracellular space. SIRT2 is secreted by macrophages following toll-like receptor (TLR) family member TLR4 or TLR2 activation. TLR-activated SIRT2 undergoes autophagosome translocation. TNF receptor associated factor 6 (TRAF6)-mediated autophagy flux in response to TLR2/4 activation can then pump SIRT2 into the microenvironment to function as extracellular SIRT2 (eSIRT2). In the extracellular space, eSIRT2 deacetylates ITGB3 on aK416 involved in cell attachment and migration, leading to a promotion of cancer cell metastasis. In lung cancer patients, significantly increased serum eSIRT2 level correlates with dramatically decreased ITGB3-K416 acetylation in cancer cells. Thus, the extracellular space is a subcellular organelle-like arena where eSIRT2 promotes cancer cell metastasis via catalyzing extracellular protein deacetylation.

The Value of the 8th Edition of American Joint Committee on Cancer Pathological Prognostic Staging on the Selection of Postmastectomy Radiotherapy for T1-2N1 Breast Cancer.

Methods and Materials: Patients diagnosed with pT1-2N1M0 breast cancer between 2008 and 2018 in West China Hospital, Sichuan University were included. Locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS) were defined as endpoints. The propensity score matching (PSM), receiver operating characteristic (ROC) curve, the Kaplan-Meier analysis, and the Cox multivariable model were used for data analysis. Results: We identified 1,615 patients with T1-2N1M0 breast cancer, and 44.9% (n = 744) of them were treated with PMRT. With a median follow-up of 76 months, 46 (2.8%) recurrences, 96 (5.9%) deaths, and 80 (5.0%) breast cancer-related deaths occurred. The 5-year LRFS, DMFS, DFS, BCSS, and OS were 98.6%, 95.3%, 93.7%, 96.5%, and 96.0%, respectively. PMRT could not improve 5-year LRFS, DMFS, DFS, BCSS, and OS compared with non-PMRT neither before nor after PSM in the era of contemporary systemic treatment. ROC curve showed that the 8th pathological prognostic staging had better discriminative ability compared with the 7th anatomical staging [the area under the curve (AUC) 0.653 vs. 0.546, P < 0.001]. In the anatomical staging system, PMRT had comparable 5-year BCSS in comparison with non-PMRT both in stages IIA (97.4% vs. 96.8%, P = 0.799) and IIB (95.3% vs. 97.0%, P = 0.071). When stratified according to the pathological staging, PMRT was associated with better 5-year BCSS in stage IIB (97.1% vs. 90.7%, P = 0.039), while not in stages IA, IB, IIA, and IIIA. Multivariate analysis demonstrated that PMRT was a significantly protective factor for BCSS in stage IIB (HR 0.331, 95% CI: 0.100-0.967, P = 0.044). Conclusion: The new staging could better select high-risk patients with T1-2N1 breast cancer for radiotherapy compared with the 7th staging, and PMRT might be exempted except the 8th staging of IIB in the era of contemporary systemic therapy in this disease.

Effect of long-term valproic acid therapy on lipid profiles in paediatric patients with epilepsy: a meta-analysis

Objective: Despite the potential role of valproic acid (VPA) in weight gain, the effects of VPA therapy on lipid profiles remain unclear. This study aimed to review the influence of VPA therapy on serum lipid profiles in children with epilepsy. Methods: This meta-analysis was conducted on data from PubMed, Web of Science, Cochrane Library, and Embase databases. Case-controlled studies, which assessed the effects of VPA therapy on lipid profiles, were included. All outcomes were recorded as continuous variables, and the effect size was measured. Results: VPA therapy was associated with a significant reduction in total cholesterol (mean difference [MD]=-6.34, 95% confidence interval [CI]: -12.30, -0.37, p=0.04) and low-density lipoprotein cholesterol levels (MD = -7.75, 95% CI: -13.48, -2.0, p=0.008). No significant effects were observed regarding the levels of high-density lipoprotein cholesterol and triglycerides. Significance: In conclusion, this meta-analysis indicates that VPA therapy causes a decrease in the levels of total cholesterol and low-density lipoprotein cholesterol.

Tetramethylpyrazine Improves Monocrotaline-Induced Pulmonary Hypertension through the ROS/iNOS/PKG-1 Axis.

Background: Tetramethylpyrazine (TMP), a potent anti-free radical and anti-inflammations substance, has been demonstrated to possess a direct vessel relaxation property. This study aimed to evaluate the effect of TMP treatment in pulmonary hypertension (PH) and test the hypothesis that TMP prevents or reverses the process of PH. Methods: Rats (n = 36) injected with 50 mg/kg of monocrotaline (MCT) subcutaneously 4 weeks to develop PH were then randomized to TMP (5 mg/kg per day) for another 4 weeks. Hemodynamics was evaluated via the right ventricle. Pulmonary vessels structural remodeling and inflammation were examined by histologic and transmission electron microscopy observation. The expression of inducible nitric oxide synthase (iNOS) and cGMP-dependent protein kinases 1 (PKG-1) was detected by immunohistochemical staining and Western blot. Generation of reactive oxygen species (ROS) and antioxidation species was measured by biochemical analyses. Results: MCT increased PH and right ventricle hypertrophy. TMP alleviated pulmonary arterial pressure elevation, leukocyte infiltration, and structural remodeling of pulmonary arterials induced by MCT successfully. TMP treatment significantly increased the PKG-1 expression and suppressed the iNOS expression. The activity of superoxide dismutase (SOD), glutathione peroxidase (GSH), and catalase (CAT) was significantly higher than control group, while malondialdehyde (MDA) levels were lower compared with MCT group. Conclusion: TMP can suppress established MCT-induced PH through the ROS/iNOS/PKG axis. The underlying mechanisms may be associated with its anti-inflammatory, antioxidant, and antiproliferative properties in pulmonary arterial.

Are patients recovering from Kawasaki disease at increased risk for accelerated atherosclerosis? A meta-analysis.

BACKGROUND: Recent studies have suggested that Kawasaki disease (KD) may cause endothelial dysfunction, which can potentially induce atherosclerosis. However, there is still no consensus on the relationship between KD and atherosclerosis. This article aimed to determine whether patients with a history of KD may be at increased risk for accelerated atherosclerosis via a meta-analysis. METHODS: The PubMed, Embase, and SpringerLink databases were systematically searched. Studies on risk factors for atherosclerosis were included. A meta-analysis of case-control studies was performed using RevMan 5.3 software. RESULTS: Twenty studies were included with a total of 1684 subjects (990 patients after KD and 694 controls). The meta-analysis showed that the level of carotid intima-media thickness (cIMT) (95% CI: 0.01, 0.03; P = 0.005) and high-sensitivity C-reactive protein (hsCRP) (95% CI: 0.00, 0.10; P = 0.03) were significantly higher in patients after KD than controls, whereas flow-mediated dilatation (FMD) (95% CI: - 5.14, - 1.26; P = 0.001) in patients after KD was significantly lower. There were no significant differences in total cholesterol (TC) (95% CI: - 0.13, 5.92; P = 0.06), low-density lipoprotein cholesterol (LDL) (95% CI: - 0.65, 2.08; P = 0.31), or triglycerides (TG) (95% CI: - 1.94, 8.03; P = 0.23). CONCLUSION: Endothelial dysfunction and inflammatory processes may exist in patients with a history of KD, which are risk factors for the development of atherosclerosis.

A clear trade-off between leaf hydraulic efficiency and safety in an aridland shrub during regrowth.

It has been suggested that a trade-off between hydraulic efficiency and safety is related to drought adaptation across species. However, whether leaf hydraulic efficiency is sacrificed for safety during woody resprout regrowth after crown removal is not well understood. We measured leaf water potential (ψleaf ) at predawn (ψpd ) and midday (ψmid ), leaf maximum hydraulic conductance (Kleaf-max ), ψleaf at induction 50% loss of Kleaf-max (Kleaf P50 ), leaf area-specific whole-plant hydraulic conductance (LSC), leaf vein structure and turgor loss point (πtlp ) in 1- to 13-year-old resprouts of the aridland shrub (Caragana korshinskii). ψpd was similar, ψmid and Kleaf P50 became more negative, and Kleaf-max decreased in resprouts with the increasing age; thus, leaf hydraulic efficiency clearly traded off against safety. The difference between ψmid and Kleaf P50 , leaf hydraulic safety margin, increased gradually with increasing resprout age. More negative ψmid and Kleaf P50 were closely related to decreasing LSC and more negative πtlp , respectively, and the decreasing Kleaf-max arose from the lower minor vein density and the narrower midrib xylem vessels. Our results showed that a clear trade-off between leaf hydraulic efficiency and safety helps C. korshinskii resprouts adapt to increasing water stress as they approach final size.

The Clinical Effect of Repetitive Transcranial Magnetic Stimulation on the Disturbance of Consciousness in Patients in a Vegetative State.

OBJECTIVE: To explore the effect of combining repetitive transcranial magnetic stimulation (rTMS) and conventional rehabilitation on the recovery of consciousness in patients in a persistent vegetative state (PVS). METHODS: A total of 48 patients in a PVS were randomly divided into a treatment and control group. Patients in the treatment group were treated with rTMS to stimulate the dorsolateral prefrontal cortex, and patients in the control group were treated with false stimulation. All patients were evaluated using scales and neuroelectrophysiological assessment before treatment, after 30 days of treatment, and following 60 days of treatment. RESULTS: Based on the Coma Recovery Scale-Revised (CRS-R) and electroencephalogram (EEG) grading indexes, the treatment group was significantly higher than those of the control group after 30 and 60 days of treatment. The average difference in the three measurements between the two groups before treatment, at 30 days, and 60 days was 0.04, 1.54, and 2.09 for CRS-R and 0.08, -0.83, and -0.62 for EEG indexes, respectively. The latency periods of each wave of the brainstem auditory evoked potentials (BAEPs) in the treatment group were shorter than those in the control group after 30 and 60 days of treatment. In both groups, the BAEP scores after 30 days of treatment were significantly higher than the scores before treatment, and the scores after 60 days of treatment were higher than the scores after 30 days. CONCLUSION: In patients in a PVS, rTMS assists in the recovery of consciousness function.

An Update on Cardiovascular Risk Factors After Kawasaki Disease.

First described in Japan 50 years ago, Kawasaki disease is a worldwide multisystem disease. It is an acute self-limited vasculitis of unknown etiology that can lead to coronary artery lesions, such as dilatation, aneurysms, and stenosis in children. It is one of the common causes of acquired heart disease among children in developed countries. The coronary aneurysm is a severe complication in the acute stage, possibly leading to stenotic lesions or myocardial ischemia. More concerns have centered on endothelial damage and the early onset of atherosclerosis in patients with KD. Although the coronary artery aneurysm is small or degenerated, the vascular structure does not return to normal, vascular endothelial dysfunction and remodeling continue. Most patients diagnosed with coronary artery sequelae are at risk of long-term complications. There are still many unknown aspects regarding the long-term prognosis of patients. Concerns have centered on the early onset of atherosclerosis in patients with KD. There is still no consensus on the relationship between Kawasaki disease and atherosclerosis. This study aimed to evaluate if patients with a history of KD were at risk of accelerated atherosclerosis.

Comparing the 7th and 8th editions of UICC/AJCC staging system for nasopharyngeal carcinoma in the IMRT era.

BACKGROUND: To compare the prognostic value of 7th and 8th editions of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system for patients with nonmetastatic nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy and simultaneous integrated boost- intensity-modulated radiation therapy (SIB-IMRT). METHODS: Patients with NPC (n = 300) who received SIB-IMRT were included. Survival by T-classification, N-classification, and stage group of each staging system was assessed. RESULTS: For T-classification, nonsignificant difference was observed between T1 and T3 and between T2 and T3 disease (P = 0.066 and 0.106, respectively) for overall survival (OS) in the 7th staging system, whereas all these differences were significant in the 8th staging system (all P < 0.05). The survival curves for disease-free survival (DFS) and locoregional recurrence-free survival (LRRFS) in both staging systems were similar, except for the comparison of T2 and T4 disease for LRRFS (P = 0.070 for 7th edition; P = 0.011 for 8th edition). For N-classification, significant differences were observed between N2 and N3 diseases after revision (P = 0.046 and P = 0.043 for OS and DFS, respectively). For staging system, no significant difference was observed between IVA and IVB of 7th edition. CONCLUSION: The 8th AJCC staging system appeared to have superior prognosis value in the SIB-IMRT era compared with the 7th edition.

Stomatal morphology and physiology explain varied sensitivity to abscisic acid across vascular plant lineages.

Abscisic acid (ABA) can induce rapid stomatal closure in seed plants, but the action of this hormone on the stomata of fern and lycophyte species remains equivocal. Here, ABA-induced stomatal closure, signaling components, guard cell K+ and Ca2+ fluxes, vacuolar and actin cytoskeleton dynamics, and the permeability coefficient of guard cell protoplasts (Pf) were analyzed in species spanning the diversity of vascular land plants including 11 seed plants, 6 ferns, and 1 lycophyte. We found that all 11 seed plants exhibited ABA-induced stomatal closure, but the fern and lycophyte species did not. ABA-induced hydrogen peroxide elevation was observed in all species, but the signaling pathway downstream of nitric oxide production, including ion channel activation, was only observed in seed plants. In the angiosperm faba bean (Vicia faba), ABA application caused large vacuolar compartments to disaggregate, actin filaments to disintegrate into short fragments and Pf to increase. None of these changes was observed in the guard cells of the fern Matteuccia struthiopteris and lycophyte Selaginella moellendorffii treated with ABA, but a hypertonic osmotic solution did induce stomatal closure in fern and the lycophyte. Our results suggest that there is a major difference in the regulation of stomata between the fern and lycophyte plants and the seed plants. Importantly, these findings have uncovered the physiological and biophysical mechanisms that may have been responsible for the evolution of a stomatal response to ABA in the earliest seed plants.

The comparison of prognostic value of tumour volumetric regression ratio and RECIST 1.1 criteria after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: To compare the prognostic value of the sum volumetric regression ratio (SVRR) of the primary tumour and metastatic lymph nodes with treatment response based on RECIST 1.1 criteria after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: A total of 117 stage III-IVA NPC patients treated with induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) were retrospectively reviewed. The SVRR and the treatment response based on RECIST 1.1 were measured using contrast-enhanced computed tomography (CT) localisations before and after induction chemotherapy. The receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff point of the SVRR and compare the prognostic value of the SVRR and RECIST 1.1criteria. RESULTS: The optimal cutoff points of SVRR for progression-free survival (PFS), locoregional failure-free survival (LRFFS) and distant metastasis-free survival (DMFS) were all 25.15%, while for overall survival (OS) it was 16.63%. The area under the ROC curve (AUC) of optimal cutoff points of SVRR was superior than that of RECIST 1.1 for PFS (AUC: 0.716 vs. 0.578; P = 0.0022), LRFFS (AUC: 0.700 vs. 0.574; P = 0.0080) and DMFS (AUC: 0.736 vs. 0.606; P = 0.0053), respectively. The 3-year PFS, DMFS and OS rates for SVRR less than vs. greater than or equal to the cutoff points were 55.8% vs. 92.2% (P < 0.001, hazard ratio (HR): 0.209, 95% confidence interval (CI): 0.091-0.480), 59.7% vs. 96.7% (P < 0.001, HR: 0.120, 95% CI: 0.043-0.336) and 66.7% vs. 98.1% (P < 0.001, HR: 0.069, 95% CI: 0.014-0.342), while the responses [stable disease (SD), partial response (PR)] based on RECIST 1.1 were not significantly associated with 3-year survival rates. Multivariate analysis indicated that SVRR was an independent prognostic factor for PFS, DMFS and OS (all P < 0.05). CONCLUSIONS: The sum volumetric regression ratio and response based on RECIST 1.1 were related to the prognosis in locoregionally advanced NPC after induction chemotherapy. Sum volumetric regression ratio is an independent outcome predictor for survival in locoregionally advanced NPC, playing a better prognostic role than RECIST 1.1.

Primary radical hysterectomy vs chemoradiation for IB2-IIA cervical cancer: A systematic review and meta-analysis.

BACKGROUND: To compare the clinical outcomes of radical hysterectomy (RH) with chemoradiotherapy (CRT) in women with stage IB2-IIA cervical cancer. METHODS: Based on articles published up to December 2017, a literature search of PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese National Knowledge Infrastructure (CNKI) databases was conducted to identify eligible studies. Overall survival (OS), progression-free survival (PFS) with hazard ratios (HRs), and toxicities with odds ratios (ORs) were analyzed. RESULTS: In total, 7 studies comprising 687 patients were identified for this meta-analysis. RH showed a significant trend toward improved survival outcomes compared with those of CRT, regardless of OS (HR = 0.49, 95% confidence interval [CI] 0.36-0.67, P < .001); or PFS (1.61, 95% CI 1.15-2.26, P = .005) for IB2-IIA cervical cancer. Subgroup analysis revealed that stage IB2 cervical cancer patients obtained better OS (HR = 0.36, 95% CI 0.23-0.56, P < .001; heterogeneity: P = .32, I = 13%). However, a higher incidence of grade 3/4 genitourinary abnormalities was evident with RH (OR = 2.3, 95% CI 1.42-3.87, P = .021). CONCLUSION: Our study suggested that RH had distinct advantages over CRT for carcinoma of the uterine cervix with FIGO stage IB2-IIA, especially for IB2 cervical cancer.

[Shensong Yangxin Capsules in the adjuvant treatment of stable angina pectoris:a Meta-analysis and trial sequential analysis].

To systemically evaluate the benefits and side effects of Shensong Yangxin Capsules( SYC) in the adjuvant treatment of stable angina pectoris( SAP). Chinese and English databases( PubMed,EMbase,the Cochrane Library,CBM,CNKI,VIP,Wan Fang database) were retrieved to collect the randomized controlled trials( RCTs) about therapeutic efficacy of SYC combined with routine drug( trial group) vs routine drug( control group) in the treatment of SAP. The methodological quality of the RCTs was evaluated based on the cochrane risk of bias assessment tool. The data were extracted and Meta-analyzed by Reviewer Manager 5. 3. TSA 0. 9 software was used for trial sequential analysis( TSA) of the total effective rate of symptoms improvement. A total of 15 RCTs with 1 316 participants were included. RESULTS:: of Meta-analysis showed that the total effective rate of angina symptoms improvement( RR = 1. 15,95% CI[1. 09,1. 21],P<0. 001) of trial group were significantly higher than those of control group,with statistical significance,the total effective rate of electrocardiograms( ECG) improvement( RR = 1. 10,95% CI[0. 94,1. 29],P = 0. 25) of trial group were significantly higher than those of control group,but the difference was not statistically significant. After treatment,the improvement of the total time of 24 h general ischemia( SMD =-1. 21,95%CI[-1. 97,-0. 45],P = 0. 002),the ST-segment depression amplitude( SMD =-1. 30,95%CI [-1. 52,-1. 09],P<0. 001),the duration of angina pectoris attack( SMD =-1. 16,95% CI[-1. 36,-0. 95],P< 0. 001),the angina pectoris attack every week( SMD =-0. 80,95%CI[-1. 10,-0. 50],P<0. 001),the onsumption of nitroglycerin every week( SMD=-0. 72,95%CI[-1. 05,-0. 39],P<0. 001) in the trial group were better than that of the control group,and the difference was statistically significant. Besides,the improvement of the blood lipid and high sensitivity C reactive protein( hs-CRP) in the trial group were better than those of the control group after treatment,and the difference was statistically significant( P< 0. 001). Funnel plots and Egger's linear regression showed that there was no publication bias. By sensitivity analysis,it showed that the results of this study were stable and reliable. No obvious adverse drug reactions were observed in all studies. TSA analysis showed that the evidence of Meta-analysis was reliable. SYC combined with routine Western medicine treatment for SAP can improve the total effective rate of angina pectoris,reduce 24 h total ischemia time,ST segment depression amplitude,duration of angina pectoris attack,frequency of angina pectoris attack and nitroglycerin dosage,and also can improve blood lipid and hs-CRP levels.

The prognostic value of volumetric reduction of the target lesions after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: We explored whether the volumetric reduction ratio of target lesion after induction chemotherapy (IC) had any prognostic value in nasopharyngeal carcinoma (NPC). METHODS: From 2013 to 2016, 72 NPC patients treated with PCF (paclitaxel, cisplatin, 5-fluorouracil) IC followed by cisplatin-based concurrent chemoradiotherapy were analyzed. The volumes of target lesions before and after IC and survival conditions were assessed. RESULTS: For all cases, volumetric reduction ratios of the total tumor load ≥ optimal cutoff values were significantly associated with increased 2-year progression-free survival, locoregional failure-free survival, and distant metastasis-free survival (DMFS) rates, and for cervical lymph nodes, the volumetric reduction ratio ≥ optimal cutoff value was significant for DMFS (all P < .05). Accordingly, the optimal cutoff values were 24.56% (AUC = 60.5%), 23.91% (AUC = 57.7%), 29.77% (AUC = 75.8%), and 34.17% (AUC = 62.5%), respectively. CONCLUSION: Volumetric reductions of target lesions after IC are independent survival predictors for NPC, especially for those with N2/N3 disease.