Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial.

BACKGROUND: Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). RESULTS: A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802). CONCLUSIONS: NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.

Observation of the Exotic 0_{2}

We report here the first observation of the 0_{2}^{+} state of ^{8}He, which has been predicted to feature the condensatelike α+^{2}n+^{2}n cluster structure. We show that this state is characterized by a spin parity of 0^{+}, a large isoscalar monopole transition strength, and the emission of a strongly correlated neutron pair, in line with theoretical predictions. Our finding is further supported by the state-of-the-art microscopic α+4n model calculations. The present results may lead to new insights into clustering in neutron-rich nuclear systems and the pair correlation and condensation in quantum many-body systems under strong interactions.

[The standardized diagnosis and treatment of rheumatoid arthritis].

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation of the joints with high risk of disability. In recent years, remarkable progress has been made towards the diagnosis and treatment of RA, and the international RA guidelines have been also kept updated. Nevertheless, there are many challenges in China, especially inadequate number of rheumatologists and insufficient experience in the diagnosis and treatment of RA. Therefore, Chinese Rheumatology Association drafted the standardized diagnosis and treatment of RA based on the available evidence, so as to improve the management of RA patients in China.

Proton Shell Evolution below

The ß-delayed γ-ray spectroscopy of neutron-rich ^{123,125}Ag isotopes is investigated at the Radioactive Isotope Beam Factory of RIKEN, and the long-predicted 1/2^{-} ß-emitting isomers in ^{123,125}Ag are identified for the first time. With the new experimental results, the systematic trend of energy spacing between the lowest 9/2^{+} and 1/2^{-} levels is extended in Ag isotopes up to N=78, providing a clear signal for the reduction of the Z=40 subshell gap in Ag towards N=82. Shell-model calculations with the state-of-the-art V_{MU} plus M3Y spin-orbit interaction give a satisfactory description of the low-lying states in ^{123,125}Ag. The tensor force is found to play a crucial role in the evolution of the size of the Z=40 subshell gap. The observed inversion of the single-particle levels around ^{123}Ag can be well interpreted in terms of the monopole shift of the π1g_{9/2} orbitals mainly caused by the increasing occupation of ν1h_{11/2} orbitals.

Mifepristone alleviates cerebral ischemia-reperfusion injury in rats by stimulating PPAR γ.

OBJECTIVE: To investigate the changes of peroxisome proliferator-activated receptor gamma (PPAR γ) in focal cerebral ischemia-reperfusion injury, and to explore the effect and mechanism of mifepristone on the cerebral ischemia-reperfusion injury. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats were selected, and the middle cerebral artery occlusion and reperfusion (MCAO/R) rat model was constructed using the longa's suture-occluded method. The sham operation group was not inserted with occlusion sutures. All experimental rats were divided into four groups: the sham operation group (SHA group), the MCAO/R model group (MCR group), the mifepristone intervention group (MIF group) (3 mg/kg, intragastric administration), and the mifepristone + bisphenol A diglycidyl ether (BADGE) intervention group (MIF+BAD group) [3 mg/kg mifepristone (intragastric administration) + 30 mg/kg BADGE (intraperitoneal injection)]. The long's scoring method (5 grades) was applied for scoring after reperfusion, at the time when the animals woke up, and at 48 h after awaking before execution, respectively. 48 h after the model was successfully established, triphenyl tetrazolium chloride (TTC) staining was performed to calculate the volume of cerebral infarction, and Nissl staining was conducted to observe the cranial nerve tissue morphology. Meanwhile, immune-histochemical staining was used to detect PPAR γ. Moreover, the protein expression levels of PPAR γ, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), matrix metalloproteinase-2 (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase 1 (TIMP-1) were examined by Western blotting (WB). RESULTS: Mifepristone could significantly enhance the neurological function after cerebral ischemia-reperfusion injury, reduce the volume of cerebral infarction, and improve the morphology of nerve tissues in rats. The expression of PPAR γ in the brain tissues of rats after cerebral ischemia-reperfusion injury markedly declined, whereas mifepristone could remarkably increase the protein expression of PPAR γ. After mifepristone intervention, the protein levels of TNF-α, IL-1ß, IL-6, MMP-2, and MMP-9 in the infarcted brain tissues of rats were markedly decreased, while the expression of the TIMP-1 protein was increased. When combined with BADGE, the effect of mifepristone was partially offset. CONCLUSIONS: Mifepristone acts as a PPAR γ agonist, and relieves cerebral ischemia-reperfusion injury by restoring the balance between MMPs and TIMPs and inhibiting inflammatory cytokines.

Observation of enhanced monopole strength and clustering in (12)Be.

In a recent breakup-reaction experiment using a Be12 beam at 29 MeV/nucleon, the 0+ band head of the expected He4+He8 molecular rotation was clearly identified at about 10.3 MeV, from which a large monopole matrix element of 7.0±1.0 fm2 and a large cluster-decay width were determined for the first time. These findings support the picture of strong clustering in Be12, which has been a subject of intense investigations over the past decade. The results were obtained thanks to a specially arranged detection system around zero degrees, which is essential in determining the newly emphasized monopole strengths to signal the cluster formation in a nucleus.

Anthelmintic activity of steroidal saponins from Paris polyphylla.

The present study was undertaken to investigate the anthelmintic activity of crude extracts and pure compounds from the rhizomes of Paris polyphylla. The methanol extract showed a promising anthelmintic activity against Dactylogyrus intermedius (EC(50) value=18.06 mg l(-¹). Based on these finding, the methanol extract was fractionated on silica gel column chromatography in a bioassay-guided fractionation affording two known steroidal saponins showing potent activity, dioscin and polyphyllin D. Both dioscin and polyphyllin D exhibited significant activity against D. intermedius with EC(50) values of 0.44 and 0.70 mg l(-¹), respectively, which were more effective than the positive control, mebendazole (EC(50) value=1.25 mg l(-¹)). The acute toxicities (LC(50)) of dioscin and polyphyllin D for goldfish were 1.37 and 1.08 mg l(-¹), respectively. These results indicated that P. polyphylla extract and the isolated compounds are potential natural agents for the control of Dactylogyrus infestation. This is the first report on in vivo anthelmintic investigation for P. polyphylla.