Induction immunotherapy plus chemotherapy followed by definitive chemoradiation therapy in locally advanced esophageal squamous cell carcinoma: a propensity-score matched study.

BACKGROUND: For patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC), concurrent chemoradiotherapy (CCRT) is the current standard treatment; however, the prognosis remains poor. Immunotherapy combined with chemotherapy has demonstrated improved survival outcomes in advanced ESCC. Nevertheless, there is a lack of reports on the role of induction immunotherapy plus chemotherapy prior to CCRT for unresectable locally advanced ESCC. Therefore, this study aimed to evaluate the efficacy and safety of induction immunotherapy plus chemotherapy followed by definitive chemoradiotherapy in patients with unresectable locally advanced ESCC. METHODS: This study retrospectively collected clinical data of patients diagnosed with locally advanced ESCC who were treated with radical CCRT between 2017 and 2021 at our institution. The patients were divided into two groups: an induction immunotherapy plus chemotherapy group (induction IC group) or a CCRT group. To assess progression-free survival (PFS) and overall survival (OS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: A total of 132 patients with unresectable locally advanced ESCC were included in this study, with 61 (45.26%) patients in the induction IC group and 71 (54.74%) patients in the CCRT group. With a median follow-up of 37.0 months, median PFS and OS were 25.2 and 39.2 months, respectively. The patients in the induction IC group exhibited a significant improvement in PFS and OS in comparison with those in the CCRT group (median PFS: not reached [NR] versus 15.9 months, hazard ratio [HR] 0.526 [95%CI 0.325-0.851], P = 0.0077; median OS: NR versus 25.2 months, HR 0.412 [95%CI 0.236-0.719], P = 0.0012). After PSM (50 pairs), both PFS and OS remained superior in the induction IC group compared to the CCRT group (HR 0.490 [95%CI 0.280-0.858], P = 0.011; HR 0.454 [95%CI 0.246-0.837], P = 0.0093), with 2-year PFS rates of 67.6 and 42.0%, and the 2-year OS rates of 74.6 and 52.0%, respectively. Multivariate analysis revealed that lower tumor stage, concurrent chemotherapy using double agents, and induction immunotherapy plus chemotherapy before CCRT were associated with better prognosis. CONCLUSIONS: Our results showed for the first time that induction immunotherapy plus chemotherapy followed by CCRT for unresectable locally advanced ESCC provided a survival benefit with manageable safety profile. More prospective clinical studies should be warranted.

URP20 improves corneal injury caused by alkali burns combined with pathogenic bacterial infection in rats.

Corneal alkali burns often occur in industrial production and daily life, combined with infection, and may cause severe eye disease. Oxidative stress and neovascularization (NV) are important factors leading to a poor prognosis. URP20 is an antimicrobial peptide that has been proven to treat bacterial keratitis in rats through antibacterial and anti-NV effects. Therefore, in this study, the protective effect and influence mechanism of URP20 were explored in a rat model of alkali burn together with pathogenic bacteria (Staphylococcus aureus and Escherichia coli) infection. In addition, human umbilical vein endothelial cells (HUVECs) and human corneal epithelial cells (HCECs) were selected to verify the effects of URP20 on vascularization and oxidative stress. The results showed that URP20 treatment could protect corneal tissue, reduce corneal turbidity, and reduce the NV pathological score. Furthermore, URP20 significantly inhibited the expression of the vascularization marker proteins VEGFR2 and CD31. URP20 also reduced the migration ability of HUVECs. In terms of oxidative stress, URP20 significantly upregulated SOD and GSH contents in corneal tissue and HCECs (treated with 200 µM H2O2) and promoted the expression of the antioxidant protein Nrf2/HO-1. At the same time, MDA and ROS levels were also inhibited. In conclusion, URP20 could improve corneal injury combined with bacterial infection in rats caused by alkali burns through antibacterial, anti-NV, and antioxidant activities.

Role of dynamic contrast-enhanced MRI in predicting severe acute radiation-induced rectal injury in patients with rectal cancer.

OBJECTIVES: To explore the potential of dynamic contrast-enhanced MRI (DCE-MRI) quantitative parameters in predicting severe acute radiation-induced rectal injury (RRI) in rectal cancer. METHODS: This retrospective study enrolled 49 patients with rectal cancer who underwent neoadjuvant chemoradiotherapy and rectal MRI including a DCE-MRI sequence from November 2014 to March 2021. Two radiologists independently measured DCE-MRI quantitative parameters, including the forward volume transfer constant (Ktrans), rate constant (kep), fractional extravascular extracellular space volume (ve), and the thickness of the rectal wall farthest away from the tumor. These parameters were compared between mild and severe acute RRI groups based on histopathological assessment. Receiver operating characteristic curve analysis was performed to analyze statistically significant parameters. RESULTS: Forty-nine patients (mean age, 54 years ± 12 [standard deviation]; 37 men) were enrolled, including 25 patients with severe acute RRI. Ktrans was lower in severe acute RRI group than mild acute RRI group (0.032 min-1 vs 0.054 min-1; p = 0.008), but difference of other parameters (kep, ve and rectal wall thickness) was not significant between these two groups (all p > 0.05). The area under the receiver operating characteristic curve of Ktrans was 0.72 (95% confidence interval: 0.57, 0.84). With a Ktrans cutoff value of 0.047 min-1, the sensitivity and specificity for severe acute RRI prediction were 80% and 54%, respectively. CONCLUSION: Ktrans demonstrated moderate diagnostic performance in predicting severe acute RRI. CLINICAL RELEVANCE STATEMENT: Dynamic contrast-enhanced MRI can provide non-invasive and objective evidence for perioperative management and treatment strategies in rectal cancer patients with acute radiation-induced rectal injury. KEY POINTS: • To our knowledge, this study is the first to evaluate the predictive value of contrast-enhanced MRI (DCE-MRI) quantitative parameters for severe acute radiation-induced rectal injury (RRI) in patients with rectal cancer. • Forward volume transfer constant (Ktrans), derived from DCE-MRI, exhibited moderate diagnostic performance (AUC = 0.72) in predicting severe acute RRI of rectal cancer, with a sensitivity of 80% and specificity of 54%. • DCE-MRI is a promising imaging marker for distinguishing the severity of acute RRI in patients with rectal cancer.

Determinants of hyperparathyroidism in children after kidney transplantation.

INTRODUCTION: Hyperparathyroidism (HPT) can contribute to metabolic bone disease following kidney transplantation. We evaluated post-transplant trends in intact parathyroid hormone (iPTH) and determined predictors of HPT in pediatric kidney transplant (KTx) recipients. METHODS: In this single-center study, retrospective data were collected on 88 children from 2013 to 2019. Data collected included dialysis vintage, biochemical parameters, post-transplant trends in iPTH, 25(OH)Vitamin D levels and estimated glomerular filtration rate (eGFR ml/min/1.73 m2 ). Pre-transplant treatment for HPT was quantified with a Treatment Burden score (TB, score range: 0-100). After log-transforming skewed variables (iPTH and eGFR), multivariable linear regression was performed to determine predictors of log {iPTH} at 6 and 36 months (mo) post-transplant. RESULTS: Median age was 12.8 (range: 1.9-20.5) years, and dialysis vintage was 11.2 (range: 0.0-112.9) months. The majority were of Hispanic and African Ancestry (77.3%). Median post-transplant iPTH was 69.5 (range: 1.8-306.8) pg/ml at 6 mo with a gradual downward trend to 59.0 (range: 28.0-445.0) pg/ml at 36 mo. Significant multivariable predictors of higher log {iPTH} post-transplant included longer dialysis vintage, higher TB, and lower log{eGFR} at 6 mo, and higher TB, lower log{eGFR}, and deceased donor transplant at 36 mo. CONCLUSIONS: Recognition of risk factors for HPT and monitoring iPTH post-transplant may facilitate timely interventions to mitigate cardiovascular and bone disease in pediatric KTx recipients. KEY MESSAGE: Describe serial trends in intact PTH after kidney transplantation. Pre- and post-transplant factors that contribute to persistence or re-occurrence of hyperparathyroidism after kidney transplantation in children include longer dialysis vintage, high pre-transplant treatment burden and decreased post-transplant GFR. Recognition of these factors, and monitoring intact PTH after kidney transplantation, could facilitate timely interventions to mitigate cardiovascular and bone disease in children.

d-type peptides based fluorescent probes for "turn on" sensing of heparin.

Developing "turn on" fluorescent probes was desirable for the detection of the effective anticoagulant agent heparin in clinical applications. Through combining the aggregation induced emission (AIE) fluorogen tetraphenylethene (TPE) and heparin specific binding peptide AG73, the promising "turn on" fluorescent probe TPE-1 has been developed. Nevertheless, although TPE-1 could achieve the sensitive and selective detection of heparin, the low proteolytic stability and undesirable poor solubility may limit its widespread applications. In this study, seven TPE-1 derived fluorescent probes were rationally designed, efficiently synthesized and evaluated. The stability and water solubility were systematically estimated. Especially, to achieve real-time monitoring of proteolytic stability, the novel Abz/Dnp-based "turn on" probes that employ the internally quenched fluorescent (IQF) mechanism were designed and synthesized. Moreover, the detection ability of synthetic fluorescent probes for heparin were systematically evaluated. Importantly, the performance of d-type peptide fluorescent probe XH-6 indicated that d-type amino acid substitutions could significantly improve the proteolytic stability without compromising its ability of heparin sensing, and attaching solubilizing tag 2-(2-aminoethoxy) ethoxy) acid (AEEA) could greatly enhance the solubility. Collectively, this study not only established practical strategies to improve both the water solubility and proteolytic stability of "turn on" fluorescent probes for heparin sensing, but also provided valuable references for the subsequent development of enzymatic hydrolysis-resistant d-type peptides based fluorescent probes.

Benign goiters requiring thyroidectomy as the signal for PTEN hamartoma tumor syndrome diagnosis.

PTEN hamartoma tumor syndrome (PHTS) is a rare genetic cancer and tumor predisposition syndrome. Due to the wide spectrum of clinical manifestations and variable age at onset, the pathways leading to a PHTS diagnosis are difficult and highly variable. Many patients were found to have PHTS after a cancer diagnosis, missing the opportunity of prevention or enhanced cancer screening. This retrospective study evaluated a PHTS cohort followed in a high-risk surveillance clinic in a comprehensive cancer institution. A significant portion of the patients (60.9%, 14/23) had at least one cancer diagnosis (average age 34.6 years at diagnosis). A significant portion (78.3%, 18/23) were affected with clinically significant goiters (age 27.9 years), and many (60.9%, 14/23) had partial or total thyroidectomy (age 27.1 years). The average age at goiter diagnosis or thyroidectomy is younger than a cancer diagnosis. In 12 individuals who were affected with clinically significant goiter and cancer, all cancers were diagnosed after the thyroid disease (6.3 years). As clinically significant thyroid nodules in childhood or early young adulthood are common in PHTS, but uncommon for general population, these early onset thyroid nodules may alert the clinician to initiate PHTS-targeted evaluation and genetic testing.

Copper-Catalyzed Transamidation of Unactivated Secondary Amides via C-H and C-N Bond Simultaneous Activations.

Here, we demonstrate that α-C-H and C-N bonds of unactivated secondary amides can be activated simultaneously by the copper catalyst to synthesize α-ketoamides or α-ketoesters in one step, which is a challenging and underdeveloped transformation. Using copper as a catalyst and air as an oxidant, the reaction is compatible with a broad range of acetoamides, amines, and alcohols. The preliminary mechanism studies and density functional theory calculation indicated that the reaction process may undergo first radical α-oxygenation and then transamidation with the help of the resonant six-membered N,O-chelation and molecular oxygen plays a role as an initiator to trigger the transamidation process. The combination of chelation assistance and dioxygen selective oxygenation strategy would substantially extend the modern mild synthetic amide cleavage toolbox, and we envision that this broadly applicable method will be of great interest in the biopharmaceutical industry, synthetic chemistry, and agrochemical industry.

Selective and controllable amination and defluoroamidation of α-trifluoromethylstyrene.

We present a blueprint for the amination and defluoroamidation of α-trifluoromethylstyrene. This practical protocol presents a general method for the diversity-oriented synthesis of vicinal trifluoromethyl amines and gem-difluoro alkenes from α-trifluoromethylstyrene maintaining excellent chemoselectivity. The synthetic strategy features outstanding atom economy and wide functional group tolerance under mild reaction conditions.

Metabolic regularity of bioactive compounds in Bufei Jianpi granule in rats using ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry analysis technology.

Bufei Jianpi granule (BJG) is clinically effective for treating chronic obstructive pulmonary disease (COPD). At present, there is no report regarding the drug metabolism of BJG in vivo. This work developed an ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry method with high accuracy and sensitivity to determine drug metabolism of this compound in vivo. After continuous administration of BJG, the concentrations of 10 components in rat plasma, namely betaine, peimine, peiminine, astragaloside A, sinensetin, nobiletin, naringin, calycosin, formononetin, and magnolol, were determined at different time points. Meanwhile, the pharmacokinetic parameters and metabolic rules of these 10 components were evaluated: Cmax , 8.624-574.645 ng/mL; Tmax , 0.250-8.667 h; AUC0-t , 17.640-8947.393 ng h/mL; T1/2 , 3.405-66.014 h; mean residence time (MRT), 6.893-11.223 h. All these components possessed anti-inflammatory, antioxidant, and other biological activities to varying degrees, contributing to improving lung function, mitigating pneumonia and pulmonary fibrosis, and preventing and treating chronic obstructive pulmonary disease. Exploring the pharmacokinetic parameters and the laws of chemical components in BJG forms the scientific basis for applying the compound clinically and identifying quality markers for the control of the compound.

[Mechanism of famous classical formula Huaihua Powder in treatment of ulcerative colitis based on metabonomics].

Ultra-high performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry(UHPLC-Q-TOF-MS) was employed in this study to observe the effect of Huaihua Powder on the serum metabolites of mice with ulcerative colitis and reveal the mechanism of Huaihua Powder in the treatment of ulcerative colitis. The mouse model of ulcerative colitis was established by dextran sodium sulfate salt(DSS). The therapeutic effect of Huaihua Powder on ulcerative colitis was preliminarily evaluated based on the disease activity index(DAI), colon appearance, colon tissue morphology, and the content of inflammatory cytokines such as tumor necrosis factor-α(TNF-α), interleukin-6(IL-6), and interleukin-1ß(IL-1ß). UHPLC-Q-TOF-MS was employed to profile the endogenous metabolites of serum samples in blank control group, model group, and low-, medium-, and high-dose Huaihua Powder groups. Multivariate analyses such as principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed for pattern recognition. Potential biomarkers were screened by Mass Profiler Professional(MPP) B.14.00 with the thresholds of fold change≥2 and P<0.05. The metabolic pathways were enriched by MetaboAnalyst 5.0. The results showed that Huaihua Powder significantly improved the general state and colon tissue morphology of mice with ulcerative colitis, reduced DAI, and lowered the levels of TNF-α, IL-6, and IL-1ß in serum. A total of 38 potential biomarkers were predicted to be related to the regulatory effect of Huaihua Powder, which were mainly involved in glycerophospholipid metabolism, glycine, serine, and threonine metabolism, mutual transformation of glucuronic acid, and glutathione metabolism. This study employed metabolomics to analyze the mechanism of Huaihua Powder in the treatment of ulcerative colitis, laying a foundation for the further research.

A (3,8)-Connected Metal-Organic Framework with Bending Dicarboxylate Linkers for C2H2/CO2 Separation.

Herein, by replacement of the linear terephthalate linker with the bending 2,5-thiophenedicarboxylate (tdc2-) linker in the typical (3,9)-connected metal-organic framework, with a reduced 8-connected hydroxyl-centered trinuclear cluster, a new (3,8)-connected network, [Ni3(µ3-OH)(tdc)3(tpp)] [DZU-1; tpp = 2,4,6-tris(4-pyridyl)pyridine], was synthesized. The modified pore environment enables DZU-1 to selectively adsorb C2H2 over CO2 in an efficient manner.

Histologic and biomechanical evaluation of the thoracolumbar fascia graft for massive rotator cuff tears in a rat model.

BACKGROUND: Fascial autografts, which are easily available grafts, have provided a promising option in patients with massive rotator cuff tears. However, no fascial autografts other than the fascia lata have been reported, and the exact healing process of the fascia-to-bone interface is not well understood. The objective of this study is to histologically and biomechanically evaluate the effect of the thoracolumbar fascia (TLF) on fascia-to-bone healing. METHODS: A total of 88 rats were used in this study. Eight rats were killed at the beginning to form an intact control group, and the other rats were divided randomly into 2 groups (40 rats per group): the TLF augmentation group (TLF group) and the repair group (R group). The right supraspinatus was detached, and a 3 × 5 mm defect of the supraspinatus was created. The TLF was used to augment the torn supraspinatus in the TLF group, whereas in the R group, the torn supraspinatus was repaired in only a transosseous manner. Histology and biomechanics were assessed at 1, 2, 4, 8, and 16 weeks postoperatively. RESULTS: The modified tendon maturation score of the TLF group was higher than that of the R group at 8 weeks (23.00 ± 0.71 vs. 24.40 ± 0.89, P = .025) and 16 weeks (24.60 ± 0.55 vs. 26.40 ± 0.55, P ≤ .001). The TLF group showed a rapid vascular reaction, and the peak value appeared at 1 week. Later, the capillary density decreased, and almost no angiogenesis was observed at 8 weeks postoperatively. Immunohistochemistry results demonstrated a significantly higher percentage of collagen I in the TLF group at 4, 8, and 16 weeks (24.78% ± 2.76% vs. 20.67% ± 2.11% at 4 weeks, P = .046; 25.46% ± 1.77% vs. 21.49% ± 2.33% at 8 weeks, P = .026; 34.77% ± 2.25% vs. 30.01% ± 3.17% at 16 weeks, P = .040) postoperatively. Biomechanical tests revealed that the ultimate failure force in the TLF group was significantly higher than that in the R group at the final evaluation (29.13 ± 2.49 N vs. 23.10 ± 3.47 N, P = .022). CONCLUSIONS: The TLF autograft can promote a faster biological healing process and a better fixation strength. It could be used as an alternative reinforcement or bridging patch when the fascia lata is not appropriate or available for superior capsule reconstruction (SCR).

Tectorigenin enhances PDX1 expression and protects pancreatic ß-cells by activating ERK and reducing ER stress.

Pancreas/duodenum homeobox protein 1 (PDX1) is an important transcription factor that regulates islet ß-cell proliferation, differentiation, and function. Reduced expression of PDX1 is thought to contribute to ß-cell loss and dysfunction in diabetes. Thus, promoting PDX1 expression can be an effective strategy to preserve ß-cell mass and function. Previously, we established a PDX1 promoter-dependent luciferase system to screen agents that can promote PDX1 expression. Natural compound tectorigenin (TG) was identified as a promising candidate that could enhance the activity of the promoter for the PDX1 gene. In this study, we first demonstrated that TG could promote the expression of PDX1 in ß-cells via activating extracellular signal-related kinase (ERK), as indicated by increased phosphorylation of ERK; this effect was observed under either normal or glucotoxic/lipotoxic conditions. We then found that TG could suppress induced apoptosis and improved the viability of ß-cells under glucotoxicity and lipotoxicity by activation of ERK and reduction of reactive oxygen species and endoplasmic reticulum (ER) stress. These effects held true in vivo as well: prophylactic or therapeutic use of TG could obviously inhibit ER stress and decrease islet ß-cell apoptosis in the pancreas of mice given a high-fat/high-sucrose diet (HFHSD), thus dramatically maintaining or restoring ß-cell mass and islet size, respectively. Accordingly, both prophylactic and therapeutic use of TG improved HFHSD-impaired glucose metabolism in mice, as evidenced by ameliorating hyperglycemia and glucose intolerance. Taken together, TG, as an agent promoting PDX1 expression exhibits strong protective effects on islet ß-cells both in vitro and in vivo.

[3 + 2 + 1] Pyridine Skeleton Synthesis Using Acetonitrile as C4N1 Units and Solvent.

The first [3 + 2 + 1] methodology for pyridine skeleton synthesis via cascade carbopalladation/cyclization of acetonitrile, arylboronic acids, and aldehydes was developed. This reaction proceeds via six step tandem reaction sequences involving the carbopalladation reaction of acetonitrile, a nucleophilic addition, a condensation, an intramolecular Michael addition, cyclization, and aromatization. Delightfully, both palladium acetate and supported palladium nanoparticles catalyzed this reaction with similar catalytic performance. The characterization results of the fresh and used supported palladium nanoparticle catalysts indicated that the reaction might be performed via a Pd(0)/Pd(II) catalytic cycle that began with Pd(0). Furthermore, the products showed good fluorescence characteristics. The green homogeneous/heterogenous catalytic methodologies pave a new way for constructing the pyridine skeleton.

Qualitative, quantitative, and pharmacokinetic study on the absorbed components of Ardisia japonica (Thunb.) Blume in rat plasma based on molecular networking combined with quadrupole time-of-flight LC/MS and triple quadrupole LC/MS.

Isolation and screening of different compounds from plant extracts are always the key for natural drug research, and the absorbed prototype components have been considered as potential active ingredients. UHPLC combined with quadrupole time-of-flight mass spectrometry (Q-TOF-LC/MS) has been widely used in the research of natural drugs; however, we still need a more effective tool to compare and treat from a raw data. In this study, we provided a fast analytical method to measure the absorbed prototype components and their metabolites both qualitatively and quantitatively based on molecular networking (MN). For example, in Ardisia japonica (Thunb.) Blume, a total of eight absorbed prototype components in rat plasma were identified. Furthermore, pharmacokinetic study was also successfully performed on the eight absorbed prototype components in rat plasma. Our findings have provided important information on the investigation of A. japonica in vivo. More importantly, the MS network analysis pattern serves as an integral solution for qualitative and quantitative determination of phytochemical compounds in natural drugs.

[Systematic review and Meta-analysis of efficacy and safety of Compound Glycyrrhizin Injection in improving chronic hepatitis B liver damage].

To evaluate the efficacy and safety of Compound Glycyrrhizin Injection(CGI) in improving liver damage in chronic hepatitis B(CHB). PubMed, Web of Science, SinoMed, CNKI, Wanfang and VIP databases were retrieved from their inception to February 10, 2020. The randomized controlled trial(RCT) of CGI in the treatment of CHB was included. Data were independently extracted by two authors, and the methodological quality was evaluated using the Cochrane bias risk assessment tool by other two authors. Statistical analysis was performed using RevMan 5.3 software. A total of 18 two-armed RCTs were included, involving 1 915 participants. The methodological quality of all studies included was generally low. In the comparison between CGI and diammonium glycyrrhizinate, the results showed that CGI was superior to the control group in improving the overall clinical effectiveness, but there was no statistical difference between the two groups in increasing ALT normalization rate, reducing ALT and AST level. In the comparison between CGI and diammonium glycyrrhizinate+other general hepatoprotective drugs, the results showed that CGI was superior to the control group in reducing AST level, while there was no statistical difference between the two groups in reducing ALT level and increasing overall clinical effectiveness. In the comparison between CGI+other commonly used drugs(including energy mixture, glutathione, vitamins, potassium magnesium aspartate) and diammonium glycyrrhizinate+other commonly used drugs, the results showed that CGI combined with other commonly used drugs was better than the control group in reducing ALT and AST level and improving the clinical total effective rate, and there was no statistical difference between the two groups in increasing the rate of ALT normalization. In the comparison between CGI+other commonly used drugs and other commonly used drugs, the results showed that CGI combined with other commonly used drugs was superior to the control group in reducing ALT and AST level and improving the overall clinical effectiveness. In the comparison between CGI+vitamins and diammonium glycyrrhizinate+potassium magnesium aspartate+vitamins, the results showed no statistical difference between the two groups in reducing AST level. A small number of studies included reported that CGI caused mild adverse reactions when used alone or in combination with other drugs. Based on the results, CGI has a certain effect in improving CHB liver damage, but the evidence is not enough to prove that CGI would cause serious adverse events. In the future, more well-designed and strictly-enforced RCT with an adequate sample size are needed to further evaluate the effect CGI in alleviating CHB liver damage.

Final report of a prospective randomized study on thoracic radiotherapy target volume for limited-stage small cell lung cancer with radiation dosimetric analyses.

BACKGROUND: The thoracic radiotherapy (TRT) target volume for limited-stage small-cell lung cancer (SCLC) has been controversial for decades. In this report, the final results of a prospective randomized trial on the TRT target volume before and after induction chemotherapy are presented. METHODS: After 2 cycles of etoposide and cisplatin, patients arm were randomized to receive TRT to the postchemotherapy or prechemotherapy tumor volume in a study arm and a control arm. Involved-field radiotherapy was received in both arms. TRT consisted of 1.5 grays (Gy) twice daily in 30 fractions to up to a total dose of 45 Gy. Lymph node regions were contoured, and intentional and incidental radiation doses were recorded. RESULTS: The study was halted early because of slow accrual. Between 2002 and 2017, 159 and 150 patients were randomized to the study arm or the control arm, respectively; and 21.4% and 19.1% of patients, respectively, were staged using positron emission tomography/computed tomography (P = .31). With a median follow-up of 54.1 months (range, 19.9-165.0 months) in survivors, the 3-year local/regional progression-free probability was 58.2% and 65.5% in the study and control arms, respectively (P = .44), and the absolute difference was -7.3% (95% CI, -18.2%, 3.7%). In the study and control arms, the median overall survival was 21.9 months and 26.6 months, respectively, and the 5-year overall survival rate was 22.8% and 28.1%, respectively (P = .26). Grade 3 esophagitis was observed in 5.9% of patients in the study arm versus 15.5% of those in the control arm (P = .01). The isolated out-of-field failure rate was 2.6% in the study arm versus 4.1% in the control arm (P = .46), and all such failures were located in the supraclavicular fossa or contralateral hilum. The regions 7, 3P, 4L, 6, 4R, 5, and 2L received incidental radiation doses >30 Gy. CONCLUSIONS: TRT could be limited to the postchemotherapy tumor volume, and involved-field radiotherapy could be routinely applied for limited-stage SCLC.

OsSYP121 Accumulates at Fungal Penetration Sites and Mediates Host Resistance to Rice Blast.

Magnaporthe oryzae is a fungal pathogen that causes rice (Oryza sativa) blast. SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) are key components in vesicle trafficking in eukaryotic cells and are known to contribute to fungal pathogen resistance. Syntaxin of Plants121 (SYP121), a Qa-SNARE, has been reported to function in nonhost resistance in Arabidopsis (Arabidopsis thaliana). However, the functions of SYP121 in host resistance to rice blast are largely unknown. Here, we report that the rice SYP121 protein, OsSYP121, accumulates at fungal penetration sites and mediates host resistance to rice blast. OsSYP121 is plasma membrane localized and its expression was obviously induced by the rice blast in both the blast-resistant rice landrace Heikezijing and the blast-susceptible landrace Suyunuo (Su). Overexpression of OsSYP121 in Su resulted in enhanced resistance to blast. Knockdown of OsSYP121 expression in Su resulted in a more susceptible phenotype. However, knockdown of OsSYP121 expression in the resistant landrace Heikezijing resulted in susceptibility to the blast fungus. The POsSYP121 ::GFP-OsSYP121 accumulated at rice blast penetration sites in transgenic rice, as observed by confocal microscopy. Yeast two-hybrid results showed that OsSYP121 can interact with OsSNAP32 (Synaptosome-associated protein of 32 kD) and Vesicle-associated membrane protein714/724. The interaction between OsSYP121 and OsSNAP32 may contribute to host resistance to rice blast. Our study reveals that OsSYP121 plays an important role in rice blast resistance as it is a key component in vesicle trafficking.

Timing of thoracic radiotherapy is more important than dose intensification in patients with limited-stage small cell lung cancer: a parallel comparison of two prospective studies.

PURPOSE: The optimal radiotherapy dose/fraction for limited-stage small cell lung cancer (SCLC) is undefined. Our objectives were to compare efficacy between hyperfractionated thoracic radiotherapy (TRT; 1.5 Gy 2 times per day [bid] in 30 fractions) and hypofractionated TRT (2.5 Gy once per day [qd] in 22 fractions), and to explore prognostic factors influencing the prognosis, such as the timing of TRT. METHODS: Patients enrolled in two independent prospective studies were combined and analyzed. The primary endpoint was local/regional control (LRC). The prognosis was analyzed using the Cox proportional hazards regression model. RESULTS: Ninety-two and 96 patients were treated with hyperfractionated TRT and hypofractionated TRT, respectively. The 1­ and 2­year LRC rates of the two arms were 82.1 and 60.7%, and 84.9 and 68.8% (P = 0.27), respectively. The median overall survival (OS) times (months) were 28.3 (95% confidence interval, CI 16.4-40.1) and 22.0 (95% CI 16.4-27.5), while the 1­year, 3­year, and 5­year OS rates were 85.2, 40.8, and 27.1%, and 76.9, 34.3, and 26.8% (P = 0.37), respectively. Using a multivariate Cox regression study, time (days) from the initiation of chemotherapy to TRT (TCT) ≤43 was associated with improved LRC (hazard radio, HR 0.39, 95% CI 0.20-0.76; P = 0.005). Time (days) from the start of chemotherapy to the end of TRT (SER) ≤63 (HR 0.50, 95% CI 0.32-0.80; P = 0.003) and prophylactic cranial irradiation (HR 0.43; 95% CI 0.29-0.63; P = 0.000) were favorably related to OS. Grade 2/3 acute radiation esophagitis was observed in 37.0 and 17.7% of patients in the hyperfractionated and hypofractionated arms, respectively (P = 0.003). CONCLUSION: Both hyperfractionated and hypofractionated TRT schedules achieved good LRC and OS for patients with limited-stage SCLC in this study. Keeping TCT ≤43 and SER ≤63 resulted in a better prognosis. The incidence of acute esophagitis was significantly higher in the hyperfractionated arm.

Correction to: Timing of thoracic radiotherapy is more important than dose intensification in patients with limited-stage small cell lung cancer: a parallel comparison of two prospective studies.

Correction to: Strahlenther Onkol 2019 https://doi.org/10.1007/s00066-019-01539-1 The original version of this article unfortunately contained a mistake. The correct version of the funding information are given ….