Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Gouty arthritis is a condition resulting from the dysregulation of purine metabolism in the human body. It is characterized by redness, swelling, recurrent episodes of hot pain, and joint stiffness. Currently, Western medicine primarily relies on uric acid-lowering, anti-inflammatory, and analgesic drugs, but these medications often have significant side effects. In contrast, external therapies in traditional Chinese medicine are considered simpler, safer, and less likely to produce adverse reactions, thus making them more appealing to patients. This article summarizes the various external treatment methods used in traditional Chinese medicine to alleviate the clinical symptoms of gouty arthritis, offering a novel approach for clinical management.

In the era of precision medicine,patients with lung cancer receive molecular subtype-based personalized management.The un-met clinical need initiated the concept of adaptive therapy,a novel personalized treatment strategy referring to the biomarker-directed treatment escalation or de-escalation based on the standard of care,aiming to improve efficacy,quality of life,and cost efficiency.Biomark-ers are validated under specific clinical scenarios to dynamically and stably predict disease-free status or efficacy.The optimal clinical scen-arios for adaptive therapy comprises post-treatment and radiologically lesion-free or metabolically inactive disease status.Several promising clinical situations are exploring de-escalation therapy,including epidermal growth factor receptor(EGFR)-mutated,totally resected non-small cell lung cancer(NSCLC),driver gene-negative,totally resected NSCLC,driver gene-negative,radiochemotherapy-treated,locally advanced NSCLC,and drug holidays for metastatic NSCLC.Therefore,circulating tumor DNA-minimal residual disease,(ctDNA-MRD)is considered an important biomarker.Concerning escalation therapy,this field is less well-supported with results,demanding further exploration.Related to future perspectives,more effort should be invested in focusing on patients with unmet clinical needs,even those with a standard of care,and providing biomarker-based adaptive therapy for efficacy and efficiency improvement.

Though the coronavirus disease is still raging in 2021, clinical research on non-small cell lung cancer (NSCLC) did not stop. However, benefiting from advances in lung cancer treatment modality, NSCLC patients have experienced significant improvements in overall survival and quality of life. Currently, research advances on targeted therapy and immunotherapy have together transformed the status of postoperative adjuvant therapy and established a new standard treatment modality for resectable NSCLC. There are equally important research advances in locally advanced and advanced NSCLC, including new treatment modalities, new therapeutic agents, etc., all of which bringing more options for clinical treatment. These therapies will bring changes to NSCLC and will gradually lead to the chronicity of lung cancer in the foreseeable future. Therefore, this paper reviews important studies that will change clinical practice in NSCLC treatment and noteworthy research advances in 2021.
.
Carcinoma, Non-Small-Cell Lung/surgery* ; Combined Modality Therapy ; Humans ; Immunotherapy ; Lung Neoplasms/surgery* ; Quality of Life

Objective:To investigate the effect of lateral tibial periosteum distraction on diabetic foot and vasculitis foot.Methods:A retrospective analysis of 13 patients (16 feet) who received lateral tibial periosteal distraction between June 2019 and May 2020 were included in the study. 9 males and 4 females; aged 39-77 years (average 66 years); left foot 7 cases, right foot 9 cases. 5 cases were patients with diabetic foot, 1 case was diabetic foot with arteriosclerosis obliterans, 2 cases were thromboembolic vasculitis, and 5 cases were arteriosclerosis obliterans. The tibial periosteum was dissected and a distraction device was placed. In the 3 patients with foot ulcers, tibial periosteum distraction devices were placed on the severer side. The periosteal distraction began on the third day after surgery, about 0.75 mm/d, the adjustment was done usually in two weeks. Two weeks later, the stretch plate was removed surgically. The followings were evaluated: visual analogue scale (VAS) pain score, foot peripheral oxygen saturation, foot capillary filling test, lower extremity arterial CT angiography (CTA), etc.Results:All 13 patients were followed up for 2-12 weeks, with an average of 3.85 weeks. VAS pain score: the average pain score of 13 patients with preoperative foot pain was 5.31±1.84 (range, 2-9) points, and 2 weeks after surgery, the average value was 2.46±1.39 (range, 1-6) points with statistical significance ( t=6.124, P<0.001) ; peripheral foot oxygen saturation: the average preoperative blood oxygen saturation of 12 patients was 87.83%±14.83% (range, 50%-98%), 1 patient was not detected before surgery, and 2 weeks after operation, the average blood oxygen saturation was 92.33%±7.91% (range, 75%-99%). There was no significant difference between them ( t=1.124, P=0.285). The foot skin temperature of 10 patients was 35.68±0.85 ℃ (range, 34.00-36.60 ℃) before surgery and 36.23±0.46 ℃ (range, 35.50-36.90 ℃) after surgery, and the difference was statistically significant ( t=3.197, P=0.008) . Capillary filling test: 2 weeks after operation, the capillary filling response was significantly improved. All 13 patients had improved CTA of both lower extremity arteries before operation, and 11 patients had CTA taken back after two weeks of operation. Compared with preoperative CTA, new vascular network was found in the operation limb. In addition to 1 patient with thromboangiitis obliterans (mainly suffering from foot pain, no wound symptoms), 2 of 12 patients with heart failure, renal failure and other basic diseases did not heal, and the wounds of the other 10 patients had improved significantly 1 month later. Conclusion:Lateral tibia periosteum distraction can be used to treat chronic ischemic diseases of lower extremities with satisfactory postoperative results.

Objective To measure the effects of 72 h-isolation and confinement (IC)with or without sleep deprivation (SD)on attention network functions and operation performance of manual controlled rendezvous and docking task. Methods Twelve healthy male volunteers were randomly divided into 4 groups of 3.The experiments were done by means of self-control and cross-over design. Two groups underwent 72 h IC without SD,and then recovered for 7 d.After that,they underwent 72 h IC with SD.Other 2 groups underwent the identical environments in the opposite order.The evaluation of attention network functions and the functional nuclear magnetic resonance examination of brain were conducted before and after isolation.The operation performance of manual controlled rendezvous and docking task was tested during isolation.Meanwhile, the functional magnetic resonance imaging (fMRI)technology was used to evaluate the autonomic activity in the brain region. Results ①The volunteers, average reaction time, accuracy and omission rates of the attention network function test in 72 h IC had insignificant differences as compared with those before the isolation (P>0.05).The 72 h IC and SD caused average reaction time and omission rate evidently increased (t=2 .505 ,2 .3 24,P<0.05 ).For average reaction time,the main effect of test condition was obvious (F=6.725,η2=0.657,P<0.05),so as the mutual effects of test time and test condition for omission rate (F=6.057,5.906,η2=0.612,0.601,P<0.05).For accuracy rates,all three effects were not obvious (P>0.05).②The fMRI data indicated that the spontaneous nervous activity in right frontal eye field was significantly weakened by IC and SD (t=6.580,P<0.05 ),but the activities in 3 clustering fields of right temporal lobe joint were significantly enhanced (t=6.726, 4.905,8.305,P<0.05).③As compared with those in IC condition,the volunteers, success rate of manual controlled rendezvous and docking task in IC plus SD condition was evidently decreased (χ2=9 .7 6 1 ,P<0.0 1 ),but the fuel consumption,pitch angle deviation and yaw angle deviation were significantly increased (t=3 .47 5 ,3 .1 6 1 ,3 .3 7 5 ,P<0.0 1 )and the docking time was significant shortened (t=2 .6 8 1 ,P<0.0 1 ). Conclusions 72 h IC and SD has negative effects on attention network function and operation performance of manual controlled rendezvous and docking task.Sleep deprivation would be the main factor.

Objective To measure the effects of 72 h-isolation and confinement (IC)with or without sleep deprivation (SD)on attention network functions and operation performance of manual controlled rendezvous and docking task. Methods Twelve healthy male volunteers were randomly divided into 4 groups of 3.The experiments were done by means of self-control and cross-over design. Two groups underwent 72 h IC without SD,and then recovered for 7 d.After that,they underwent 72 h IC with SD.Other 2 groups underwent the identical environments in the opposite order.The evaluation of attention network functions and the functional nuclear magnetic resonance examination of brain were conducted before and after isolation.The operation performance of manual controlled rendezvous and docking task was tested during isolation.Meanwhile, the functional magnetic resonance imaging (fMRI)technology was used to evaluate the autonomic activity in the brain region. Results ①The volunteers, average reaction time, accuracy and omission rates of the attention network function test in 72 h IC had insignificant differences as compared with those before the isolation (P>0.05).The 72 h IC and SD caused average reaction time and omission rate evidently increased (t=2 .505 ,2 .3 24,P<0.05 ).For average reaction time,the main effect of test condition was obvious (F=6.725,η2=0.657,P<0.05),so as the mutual effects of test time and test condition for omission rate (F=6.057,5.906,η2=0.612,0.601,P<0.05).For accuracy rates,all three effects were not obvious (P>0.05).②The fMRI data indicated that the spontaneous nervous activity in right frontal eye field was significantly weakened by IC and SD (t=6.580,P<0.05 ),but the activities in 3 clustering fields of right temporal lobe joint were significantly enhanced (t=6.726, 4.905,8.305,P<0.05).③As compared with those in IC condition,the volunteers, success rate of manual controlled rendezvous and docking task in IC plus SD condition was evidently decreased (χ2=9 .7 6 1 ,P<0.0 1 ),but the fuel consumption,pitch angle deviation and yaw angle deviation were significantly increased (t=3 .47 5 ,3 .1 6 1 ,3 .3 7 5 ,P<0.0 1 )and the docking time was significant shortened (t=2 .6 8 1 ,P<0.0 1 ). Conclusions 72 h IC and SD has negative effects on attention network function and operation performance of manual controlled rendezvous and docking task.Sleep deprivation would be the main factor.

Objective To study the effect and mechanism of senegenin on proliferation and differentiation of neural stem cells (NSCs). Methods The primary cultured NSCs were divided into the high-dose, medium-dose, low-dose group and normal control group (NC). The complete medium containing 10, 20 and 40 μmol/L senegenin was added to senegenin low-, middle-, and high- dose groups, and the NC group was routinely cultured. After 4 days of culture, CCK8 assay was used to detect cell viability, and microscopy was performed and the number of neurospheres was counted. Western blot was used to detect the expression of Nestin, TUJ1, GSK-3β, and p-GSK-3β (Ser9), and immunofluorescence staining was used to visualized Nestin and TUJ1. Results Compared with the control group, the number of NSCs neurospheres (32.78 ± 6.30, 40.93 ± 8.34, 45.37 ± 7.96 vs. 26.48 ± 5.19) and the proliferation (127.50% ± 9.31%, 138.13% ± 6.88%, 151.25% ± 9.38% vs. 100.00% ± 5.63%) in the low-, middle- and high-doses of senegenin group significantly increased (P<0.05 or P<0.01).The expression of TUJ1(2.21 ± 0.14,3.10 ± 0.16,3.30 ± 0.15 vs.1.00 ± 0.00)in the low-,middle- and high-doses of senegenin group significantly increased (P<0.05); and the expression of Nestin (0.36 ± 0.04,0.53 ± 0.05,0.46 ± 0.05 vs.1.00 ± 0.00)significantly decreased(P<0.05).The ration of p-GSK-3β(Ser9)/GSK-3β(2.31 ± 0.17,3.41 ± 0.11,3.59 ± 0.16 vs.1.00 ± 0.00)in the low-,middle-and high-doses of senegenin group significantly increased(P<0.01).The cell number of Nestin+(50.29 ± 3.18,45.28 ± 6.23,38.72 ± 5.31 vs. 75.27 ± 6.03) in the low-, middle- and high-doses of senegenin group significantly decreased (P<0.05 or P<0.01), and the cell number of TUJ1+(32.23 ± 4.36,38.23 ± 6.01,46.23 ± 4.36 vs.20.31 ± 5.23)significantly increased (P<0.01). Conclusions The senegenin may promote the proliferation and differentiation of NSCs through the activation of Wnt pathway.

To determine the absorption properties and study the intestinal absorption kinetics of poncidin in rats. In situ single pass perfusion model was combined with High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS/MS) method to investigate the intestinal absorption characteristics and calculate absorption parameters with aspects of drug absorption, concentration and perfusion medium. The absorption of poncidin under acid condition at pH 6.5 was more stable, where intestinal enzymes showed little influence on metabolism, and the absorption was significantly higher than that in pH alkaline condition at pH 8.0 (<0.05). Drug concentrations had no significant influence on absorption rate constant of the same intestinal segment Ka and apparent permeability coefficient Papp values of poncidin. Different concentrations of poncidin showed no significant differences in the Ka and Papp values among duodenum, jejunum and colon, but the values were significantly lower than ileum absorption parameters, with significant differences (<0.05). There was no significant effect of verapamil on intestinal absorption of poncidin. The results showed that poncidin could be absorbed at all the studied intestinal segments while ileum seemed to be the best absorption segment in the concentration range of 10-1 000 μg·L⁻¹. The absorption was characterized by a linear dynamic process of passive transport, without absorption saturation. Weak acid environment was helpful for the intestinal absorption of poncidin, and ponicidin was not a substrate of P-glycoprotein (P-gp).