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

Objective:To investigate the efficacy of low-methoxyl pectin (LMP) combined with early enteral nutrition (EEN) in patients with severe acute pancreatitis (SAP) complicated by acute kidney injury (AKI).Methods:A prospective study was conducted, enrolling 85 patients with SAP complicated by AKI admitted to the First Hospital of Qinhuangdao from January 2022 to December 2023. These patients were randomized into an LMP group ( n=42) and a control group ( n=43) using a random number table. The control group received traditional EEN, while the LMP group received traditional EEN combined with LMP. Nutritional indicators [total protein (TP), albumin (Alb), and prealbumin (PA)], inflammatory markers [C-reactive protein (CRP), interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-α (TNF-α)], renal function indicators [creatinine (Cr), estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), uric acid (UA)], AKI stage, and fecal intestinal flora were compared between these two groups before and 7 days after intervention. Results:After 7 days of intervention, the TP, Alb, and PA levels significantly increased in both groups (all P<0.05); the increases in TP and PA were more significant in the LMP group (both P<0.05), whereas the increase in Alb did not differ significantly between groups ( P>0.05). The levels of CRP, IL-1, IL-6, IL-8, and TNF-α decreased significantly in both groups (all P<0.05),with more significant reductions in the LMP group (all P<0.001). The levels of Cr, eGFR, BUN, and UA improved significantly in both groups (all P<0.05),with more significant improvements in the LMP group (all P<0.05). The incidence of a higher AKI stage in the LMP group was significantly lower than that in the control group( P<0.05), and the incidence of a lower AKI stage was significantly higher than that in the control group ( P<0.001). The fecal counts of Bifidobacterium and Lactobacillus increased significantly while the fecal counts of Enterococcus and Enterobacter decreased significantly in both group (all P<0.001); notably, these changes in bacterial counts were significantly more pronounced in the LMP group ( P<0.001). Conclusions:EEN combined with LMP can significantly enhance nutritional status, reduce inflammatory response, and improve renal function in patients with SAP complicated by AKI.

In this work, starting from 4-hydroxycoumarin, three series of 22 coumarin derivatives, among which 8 have not been reported in the literature, were synthesized and their in vitro anti-inflammatory activities and mechanisms of action were preliminarily investigated using mouse macrophage model. The results showed that most of the derivatives could significantly inhibit the production of pro-inflammatory factor NO, with compounds 2e, 2f, 2g, 2h, 2i, 2j, 4e, and 4f showing better anti-inflammatory activity than the positive control drug dexamethasone. Further experiments showed that compounds 2h and 4f significantly inhibited the production of pro-inflammatory factors IL-6, TNF-α and IL-1β in RAW264.7 macrophages, and could, therefore, be used as lead compounds for further studies.

Kleine-Levin syndrome (KLS) is a rare, recurrent-remitting sleep disorder characterized by periodic hypersomnia, hyperphagia, and hypersexuality, accompanied by cognitive dysfunction, perceptual disturbances, mood changes, or psychiatric abnormalities. Patients typically experience recurrent episodes, with hypersomnic periods lasting from several days to weeks. Most KLS patients exhibit normal functions during the intermission period, while early-onset KLS cases in adolescents are rare, often presenting with frequent episodes and complex symptoms, which can easily lead to misdiagnosis. Therefore, this case report analyzed the detailed medical history, laboratory findings, differential diagnosis, and treatment of a teenage patient with KLS, along with a review of the literature. This case aims to provide a deeper understanding of the complex symptoms and diagnostic challenges associated with early-onset KLS in adolescents.

Objective:To investigate the efficacy of low-methoxyl pectin (LMP) combined with early enteral nutrition (EEN) in patients with severe acute pancreatitis (SAP) complicated by acute kidney injury (AKI).Methods:A prospective study was conducted, enrolling 85 patients with SAP complicated by AKI admitted to the First Hospital of Qinhuangdao from January 2022 to December 2023. These patients were randomized into an LMP group ( n=42) and a control group ( n=43) using a random number table. The control group received traditional EEN, while the LMP group received traditional EEN combined with LMP. Nutritional indicators [total protein (TP), albumin (Alb), and prealbumin (PA)], inflammatory markers [C-reactive protein (CRP), interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor-α (TNF-α)], renal function indicators [creatinine (Cr), estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), uric acid (UA)], AKI stage, and fecal intestinal flora were compared between these two groups before and 7 days after intervention. Results:After 7 days of intervention, the TP, Alb, and PA levels significantly increased in both groups (all P<0.05); the increases in TP and PA were more significant in the LMP group (both P<0.05), whereas the increase in Alb did not differ significantly between groups ( P>0.05). The levels of CRP, IL-1, IL-6, IL-8, and TNF-α decreased significantly in both groups (all P<0.05),with more significant reductions in the LMP group (all P<0.001). The levels of Cr, eGFR, BUN, and UA improved significantly in both groups (all P<0.05),with more significant improvements in the LMP group (all P<0.05). The incidence of a higher AKI stage in the LMP group was significantly lower than that in the control group( P<0.05), and the incidence of a lower AKI stage was significantly higher than that in the control group ( P<0.001). The fecal counts of Bifidobacterium and Lactobacillus increased significantly while the fecal counts of Enterococcus and Enterobacter decreased significantly in both group (all P<0.001); notably, these changes in bacterial counts were significantly more pronounced in the LMP group ( P<0.001). Conclusions:EEN combined with LMP can significantly enhance nutritional status, reduce inflammatory response, and improve renal function in patients with SAP complicated by AKI.

Kleine-Levin syndrome (KLS) is a rare, recurrent-remitting sleep disorder characterized by periodic hypersomnia, hyperphagia, and hypersexuality, accompanied by cognitive dysfunction, perceptual disturbances, mood changes, or psychiatric abnormalities. Patients typically experience recurrent episodes, with hypersomnic periods lasting from several days to weeks. Most KLS patients exhibit normal functions during the intermission period, while early-onset KLS cases in adolescents are rare, often presenting with frequent episodes and complex symptoms, which can easily lead to misdiagnosis. Therefore, this case report analyzed the detailed medical history, laboratory findings, differential diagnosis, and treatment of a teenage patient with KLS, along with a review of the literature. This case aims to provide a deeper understanding of the complex symptoms and diagnostic challenges associated with early-onset KLS in adolescents.

OBJECTIVE To identify the chemical constituents of the modified Yupingfengsan formula. METHODS UPLC-Q- Exactive Orbitrap-MS technology was adopted. The separation was performed on Waters BEH C18 column with acetonitrile （A）-0.1% formic acid solution （B） as mobile phase for gradient elution. The heating electrospray ionization was used for positive and negative ion mode scanning. The scanning range was m/z 50-1 500， and the spray voltage was 2 kV （positive ion mode） and 1.5 kV （negative ion mode）. The information of chemical constituents of modified Yupingfengsan formula was collected through literature review to establish a database； the structure of the constituent was identified based on the above database， relevant literature， and chromatography and mass spectrometry information of reference standards. RESULTS & CONCLUSIONS Totally 114 chemical constituents were identified from modified Yupingfengsan formula， including 31 flavonoids， 39 phenylpropanoids， 5 saponins， 8 terpenoids， 3 chromones， 3 curcuminoids， etc. Based on the comparison of reference standards， 8 constituents were ultimately determined， including magnoflorine， calycosin， calycosin glycoside， cimifugin， 5-O-methylvisammioside， sec-O- glucosylhamaudol， luteolin and mangiferin. These constituents mainly involved glycosylation cleavage， retro Diels-Alder fragmentation， glycosylation loss， neutral molecule loss and other fragmentation pathways.

Objective:To evaluate the effect of dexamethasone combined with aminophylline on perioperative airway responses in COVID-19 convalescent patients undergoing gynecological laparoscopic surgery.Methods:Sixty-eight COVID-19 convalescent patients, aged 25-57 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing gynecological laparoscopic surgery, were divided into experimental group ( n=34) and control group ( n=34). In experimental group, dexamethasone 10 mg was intravenously injected at the beginning of anesthesia induction, and aminophylline 0.25 g (in 100 ml of normal saline) was intravenously infused for 10 min starting from 15 min before the end of surgery. In control group, the equal volume of normal saline was administrated instead at the same time point. Airway secretions, laryngospasm and bronchospasm were recorded from the time point before operation to 24 h after operation, and coughing was also recorded from emergence to 3 min after extubation. The blood eosinophils (EOS) count, percentage of EOS (EOS%), and neutrophil to lymphocyte ratio were determined, and plasma C reactive protein level was measured by enzyme-linked immunosorbent assay before operation and at 24 h after operation. The serum levels of interleukin-6, tumor necrosis factor-α and interferon-γ were measured before operation, at 5 and 10 min after extubation and at 24 h after operation. Results:Compared with control group, the incidence of coughing, severity of coughing, incidence of increased airway secretion, and grade of airway secretion were significantly decreased, the levels of EOS, EOS%, neutrophil to lymphocyte ratio and plasma C reactive protein in peripheral blood and serum levels of interferon-γ, interleukin-6 and tumor necrosis factor-α were significantly decreased after operation ( P<0.05), and no significant change was found in the incidence of bronchial spasm in experimental group ( P>0.05). No laryngeal spasm occurred in both groups. Conclusions:Dexamethasone combined with aminophylline can relieve the perioperative airway responses by inhibition of inflammatory responses in COVID-19 convalescent patients undergoing gynecological laparoscopic surgery.

When performing eye movement pattern classification for different tasks, support vector machines are greatly affected by parameters. To address this problem, we propose an algorithm based on the improved whale algorithm to optimize support vector machines to enhance the performance of eye movement data classification. According to the characteristics of eye movement data, this study first extracts 57 features related to fixation and saccade, then uses the ReliefF algorithm for feature selection. To address the problems of low convergence accuracy and easy falling into local minima of the whale algorithm, we introduce inertia weights to balance local search and global search to accelerate the convergence speed of the algorithm and also use the differential variation strategy to increase individual diversity to jump out of local optimum. In this paper, experiments are conducted on eight test functions, and the results show that the improved whale algorithm has the best convergence accuracy and convergence speed. Finally, this paper applies the optimized support vector machine model of the improved whale algorithm to the task of classifying eye movement data in autism, and the experimental results on the public dataset show that the accuracy of the eye movement data classification of this paper is greatly improved compared with that of the traditional support vector machine method. Compared with the standard whale algorithm and other optimization algorithms, the optimized model proposed in this paper has higher recognition accuracy and provides a new idea and method for eye movement pattern recognition. In the future, eye movement data can be obtained by combining it with eye trackers to assist in medical diagnosis.
Animals ; Support Vector Machine ; Whales ; Eye Movements ; Algorithms

Objective To evaluate the impact of overall burden of cerebral small vessel disease(CSVD)combined with intracranial large artery atherosclerosis(ICAS)on cognitive function in very old patients.Methods A total of 178 advanced elderly patients admitted to Department of General Medicine of Wuhan Central Hospital between January 2013 and December 2022 were re-cruited in this retrospective study.According to the results of Montreal Cognitive Assessment Scale,they were divided into dementia group(n=83)and non-dementia group(n=95).All pa-tients underwent brain MRI imaging,MRI susceptibility weighted imaging and cerebral angiogra-phy.Based on these imaging findings of MRI,the effect of total burden score of CSVD and athero-sclerosis on cognition were evaluated.The volumes of 14 different gyri in the left and right brain were measured in the patients with CSVD burden score ≤2 and those ≥3.Results There were significantly more patients with numbers of microbleeding foci＞10 and lacunar foci ≥5 in the dementia group than the non-dementia group(P＜0.01).But,no statistical difference was seen in intracranial and extracranial arterial stenosis between the two groups(P＞0.05).The volumes of left and right anterior cingulate gyrus,left and right paracingulate cortex,right hippocampus,left parahippocampal gyrus,right transverse temporal gyrus and left inferior temporal gyrus were no-tably smaller in the CSVD score ≥3 group than the CSVD ≤2 group(1723.444 vs 1867.167,1590.167 vs 1595.670,1481.466 vs 1509.540,1543.831 vs 1585.505,1038.345 vs 1305.831,1220.525 vs 1392.352,P＜0.05).Conclusion Cognitive function in the advanced elderly is mainly affected by the burden of CSVD,and atherosclerotic stenosis of large arteries is not the main fac-tor affecting cognitive function.The total burden of CSVD is correlated with atrophy of some gyri.