Antibiotic resistance is spreading at a faster rate than new antibiotic agents applied for clinical remedies. It is an urgent need to discover potential compounds to combat multidrug-resistant (MDR) bacteria. Marine fungi offer a promising avenue for mining antibiotic-like molecules with chemical diversity. To discover structurally novel and antibiotic metabolites, we screened the in-house marine fungus genome library and found a fungus Stephanonectria keithii LZD-10-1 containing a non-ribosomal peptide synthetase (NRPS) cluster with 18 modules to synthesize a new subfamily of peptaibols with effective eradication against MDR pathogens. Targeting isolation of the cultured fungus afforded six new peptaibols, which exhibit the ability to kill MDR bacteria by targeting bacterial membrane phospholipids, especially phosphatidylglycerol (PG), leading to the dysfunction of bacterial membranes. Furthermore, their efficacies against methicillin-resistant Staphylococcus aureus (MRSA) in both Galleria mellonella and mouse wound infection models were observed. This study underscores the significance of employing genome-guided approaches to identify untapped marine fungi as potential sources for novel antibiotic candidates with unique scaffolds.

Objective:To predict the occurrence of chronic radiation enteritis (CRE) in cervical cancer patients by developing a prediction model based on the combination of radiomic features derived from magnetic resonance imaging (MRI) scans and clinical parameters, in order to provide a reference for clinicians to determine the prognosis of these patients and offer them individualized diagnosis and treatment.Methods:A retrospective analysis was conducted on 111 cervical cancer patients who received radical radiotherapy at the First Affiliated Hospital of Anhui Medical University. Radiological features were extracted from the T1-weighted MRI images of local lesions of cervical cancer obtained before the radiotherapy. Features were selected using the least absolute shrinkage and selection operator (LASSO) to obtain the radiomics score. The radiomics scores and clinical parameters were assessed using univariate and multivariate logistic regression analyses, followed by the establishment of nomograms. The ability of radiomics to achieve CRE prediction was assessed using the area under the curve (AUC) and the calibration and decision curves.Results:Multivariate logistic regression analysis result revealed that the independent risk factors for identifying CRE in patients included radiomics score ( HR: 17.457, 95% CI: 5.540-55.009, P<0.001), tumor volume ( HR: 3.617, 95% CI: 1.293-10.115, P=0.014), and pelvic lymph node metastasis ( HR: 3.559, 95% CI: 1.013-12.501, P=0.048). The model combining radiomics and clinical data demonstrated high performance, with its AUCs of the training and validation groups (0.888 and 0.870, respectively) higher than those of the radiomics model (0.842 and 0.804, respectively) and the clinical data model (0.721 and 0.704, respectively). The analyses of calibration and decision curves confirmed the application value of clinical radiomic nomograms. Conclusions:The model combining radiomics and clinical data allows for accurate CRE prediction. Therefore, radiomic features have the potential to serve as a promising imaging biomarker for CRE.

Objective To explore the impact of the duration of protracted abstinence(PA)treatment on the level of impulsivity among heroin addicts and to analyze the mediating effect of impulsive cognition between abstinence duration and impulsive behavior.Methods Thirty-six heroin addicts undergoing PA treatment(PA group)and forty matched healthy controls(HC)(HC group)were recruited.Demographic information was collected via questionnaires,and impulsive cognition assessments were conducted.Participants completed the GO/NOGO task to collect data on impulsive behavior.Intergroup differences were compared using the independent sample t-test,and multiple linear regression analysis and mediating effect analysis were performed on the PA group.Results The PA group exhibited significantly higher scores on motor impulsivity,non-planning impulsivity,and total impulsivity compared to the HC group.Additionally,the PA group demonstrated significantly increased NOGO error rate during the GO/NOGO task compared to the HC group(P＜0.001).Multiple linear regression analysis revealed that abstinence duration had a significant negative impact on total impulsivity and non-planning impulsivity(P＜0.001).Mediating effect analysis found a partial mediation effect of total impulsivity between abstinence duration and NOGO error rate(P＜0.001).Conclusion The PA treatment has a significant impact on the level of impulsivity among heroin addicts.Impulsive cognition play a partial mediating role between abstinence duration and impulsive behavior.These results provide an important theoretical and practical basis for optimizing PA treatment programs.

Objective:To predict the occurrence of chronic radiation enteritis (CRE) in cervical cancer patients by developing a prediction model based on the combination of radiomic features derived from magnetic resonance imaging (MRI) scans and clinical parameters, in order to provide a reference for clinicians to determine the prognosis of these patients and offer them individualized diagnosis and treatment.Methods:A retrospective analysis was conducted on 111 cervical cancer patients who received radical radiotherapy at the First Affiliated Hospital of Anhui Medical University. Radiological features were extracted from the T1-weighted MRI images of local lesions of cervical cancer obtained before the radiotherapy. Features were selected using the least absolute shrinkage and selection operator (LASSO) to obtain the radiomics score. The radiomics scores and clinical parameters were assessed using univariate and multivariate logistic regression analyses, followed by the establishment of nomograms. The ability of radiomics to achieve CRE prediction was assessed using the area under the curve (AUC) and the calibration and decision curves.Results:Multivariate logistic regression analysis result revealed that the independent risk factors for identifying CRE in patients included radiomics score ( HR: 17.457, 95% CI: 5.540-55.009, P<0.001), tumor volume ( HR: 3.617, 95% CI: 1.293-10.115, P=0.014), and pelvic lymph node metastasis ( HR: 3.559, 95% CI: 1.013-12.501, P=0.048). The model combining radiomics and clinical data demonstrated high performance, with its AUCs of the training and validation groups (0.888 and 0.870, respectively) higher than those of the radiomics model (0.842 and 0.804, respectively) and the clinical data model (0.721 and 0.704, respectively). The analyses of calibration and decision curves confirmed the application value of clinical radiomic nomograms. Conclusions:The model combining radiomics and clinical data allows for accurate CRE prediction. Therefore, radiomic features have the potential to serve as a promising imaging biomarker for CRE.

Objective To explore the impact of the duration of protracted abstinence(PA)treatment on the level of impulsivity among heroin addicts and to analyze the mediating effect of impulsive cognition between abstinence duration and impulsive behavior.Methods Thirty-six heroin addicts undergoing PA treatment(PA group)and forty matched healthy controls(HC)(HC group)were recruited.Demographic information was collected via questionnaires,and impulsive cognition assessments were conducted.Participants completed the GO/NOGO task to collect data on impulsive behavior.Intergroup differences were compared using the independent sample t-test,and multiple linear regression analysis and mediating effect analysis were performed on the PA group.Results The PA group exhibited significantly higher scores on motor impulsivity,non-planning impulsivity,and total impulsivity compared to the HC group.Additionally,the PA group demonstrated significantly increased NOGO error rate during the GO/NOGO task compared to the HC group(P＜0.001).Multiple linear regression analysis revealed that abstinence duration had a significant negative impact on total impulsivity and non-planning impulsivity(P＜0.001).Mediating effect analysis found a partial mediation effect of total impulsivity between abstinence duration and NOGO error rate(P＜0.001).Conclusion The PA treatment has a significant impact on the level of impulsivity among heroin addicts.Impulsive cognition play a partial mediating role between abstinence duration and impulsive behavior.These results provide an important theoretical and practical basis for optimizing PA treatment programs.

Objective:To optimize the extraction process of Shangke Huoxue Granule.Methods:Taking the factors of extraction solvent multiple, extraction time and extraction times as investigation factors, and extraction amount of ferulic acid, paeoniflorin and the ratio of extraction as comprehensive evaluation indices, one-factor experimental design and central composite design-response surface methodology were adopted to optimize the extraction process of Shangke Huoxue Granule.Results:The binomial fitting equation was Y=96.16+2.42 A+0.63 B-3.76 AB-1.57 A2-1.87 B2 ( P<0.01). The optimal extraction process parameters were confirmed to be adding 16 times of water, 64 minutes each time, twice. The deviation rates between the measured values of three verification experiments and the predicted value were 2.00%, 3.23% and 0.66%. Conclusion:The established model of central composite design-response surface methodology has high predictability and the optimized extraction process is stable and feasible.

[摘 要] 目的：重新评价卡瑞利珠单抗联合阿帕替尼治疗原发性肝癌（PHC）的有效性和安全性。方法：回顾性收集2019年1月至2021年5月在安徽医科大学附属第一医院确诊的PHC患者的临床资料。所有患者均接受卡瑞利珠单抗200 mg q3w联合阿帕替尼250 mg qd×21 d治疗。应用卡方检验进行基线特征比较，采用Kaplan-Meier法进行生存分析，从中估计中位总生存期（OS），然后采用Log-Rank检验进行比较；采用单因素Cox回归分析预测影响OS的因素。结果：本研究共纳入43例PHC患者，一线治疗患者的客观缓解率（ORR）为23.3%（7/30），二线及以上治疗患者的ORR为15.4%（2/13）。两组患者的疾病控制率（DCR）分别为83.3%（25/30）和61.5%（8/13），中位无进展生存期（PFS）分别为5.0个月（95% CI 3.2，6.8）和4.0个月（95% CI 1.7，6.3）（P=0.514），中位OS分别为13.0个月（95% CI 11.2，14.8）和9.0个月（95% CI 2.8，15.2）（P=0.179）。在43例患者中，33例（76.7%）存在3级或以上的治疗相关不良反应（AE）；最常见的AE为血小板计数下降（14.0%）、高血压（9.3%）和蛋白尿（9.3%）。Cox单因素回归分析显示，Child-Pugh分级是影响PHC患者预后的独立危险因素[HR=0.324，95% CI （0.146，0.716），P<0.05]。结论：卡瑞利珠单抗联合阿帕替尼可显著改善PHC患者的OS、ORR和DCR，AE可控。

Objective:To establish the TLC identification method and content determination method of ferulic acid, ligustilide, hydroxysafflor yellow A and paeoniflorin in Shangke Huoxue Decoction for quality evaluation.Methods:Ferulic acid, ligustilide, hydroxysafflor yellow A and paeoniflorin were qualitatively identified by TLC method, and the content was determined by HPLC method. Waters Symmetry ShieldTM RP18 column (4.6 mm×250 mm, 5 μm) was set, the mobile phase consisted of acetonitrile-0.15% phosphoric acid water with gradient elution at a flow of 1.0 ml/min, and the column temperature was 30 ℃.The detection wavelength was 320 nm (33-50 min for ferulic acid, 55-70 min for ligustilide), 403 nm (7-31 min for hydroxysafflor yellow A) and 230 nm (7-31 min for paeoniflorin).Results:The TLC spots were clear. The linear relationships of ferulic acid, ligustilide, and hydroxysafflor yellow A were good in the range of 3.05-48.74 μg, 3.50-26.24 μg, 21.34-213.44 μg. The method was stable, repeatable with good recovery rate.Conclusion:The TLC and HPLC method for the simutanous determination of the four effective components in Shangke Huoxue Decoction were established, and the methods are suitable for the quality evaluation of Shangke Huoxue Decoction.

Objective:To optimize the matrix formulation of Erhuang analgesic gels. Methods:Central composite design-response surface methodology was adopted to optimize the best formulation of Erhuang analgesic gels by using carbomer 940, triethanolamine and glycerine as independent variables, the appearance, stability, viscosity and in vitro release of berberine hydrochloride as comprehensive evaluation indices. Results:The fitting regressing equation was Y= 82.25 + 4.95 A+ 5.19 B + 1.41 C+ 1.51 AB + 0.904 0 AC- 0.531 9 BC- 2.92 A2-1.80 B2-0.182 1 C2. P value of the model was less than 0.000 1, and the correlation coefficient r value was 0.977. The optimal formulation of Erhuang analgesic gels consisted of 1.84% carbomer 940, 1.30 times triethanolamine of carbomer 940 and 13.99 grams of glycerine. The average comprehensive scores of three verification experiments was 88.56, and the deviations from the predicted values were 2.93%, 2.85% and 1.55%. Conclusion:The formulation process by central composite design-response surface methodology was stable and the formulation of Erhuang analgesic gels has been optimized.

Objective:To investigate the effect of GluA2-3Y which is an inhibitor of AMPA(α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid) receptor internalization on cognitive function and hippocampal postsynaptic protein expression in rats with chronic cerebral hypoperfusion.Methods:Forty-eight adult male SD rats were randomly divided into Sham group, 2VO group, high-dose GluA2-3Y group and low-dose GluA2-3Y group according to random number table, with 12 rats in each group.The chronic cerebral hypoperfusion model of rat was established by two vessel occlusion (2VO) while the Sham operation was performed in rats of Sham group.The rats in high dose GluA2-3Y group and low dose GluA2-3Y group were intraperitoneal injected with 3 μmol/kg and 0.03 μmol/kg GluA2-3Y respectively once a day for 2 weeks. Rats in 2VO group and Sham group were intraperitoneally injected with control peptide. Morris water maze test and new object recognition test were performed to evaluate the learning and memory ability of rats, and Western blot was used to evaluate the expression of Akt1、GSK3β、p-GSK3β、GluA2 and PSD-95 in rat hippocampus. The expressions of GluA2 and PSD-95 in rat hippocampus were evaluated by immunofluorescence. SPSS 23.0 software was used for data analysis. The comparison between multiple groups was analyzed by one-way ANOVA and repeated measurement ANOVA was used to analyze Morris water maze results. And independent-samples t-test was used for pairwise comparisons. Results:(1)In Morris water maze trials, the results of repeated measurement ANOVA showed that the interaction between group and time of escape latency of rats in each group was not significant ( F=0.79, P>0.05), and the group main effect and time main effect were significant ( F=24.44, 40.42, both P<0.05). On the 5th day of navigation trials, the escape latency of rats in 2VO group was longer than that in sham group ( t=5.87, P<0.05). The escape latency of rats in low dose GluA2-3Y group and high dose GluA2-3Y group were significantly shorter than that in 2VO group ( t=2.20, 3.41, both P<0.05), but there was no significant difference between low dose GluA2-3Y group and high dose GluA2-3Y group ( t=1.37, P>0.05). The target quadrant residence time and resolution coefficient ((14.57±1.40)s, (0.15±0.10)) in 2VO group were significantly lower than those in Sham group ((23.71±2.57)s, (0.40±0.06)) ( t=3.23, 2.24, both P<0.05), while the target quadrant residence time in high dose GluA2-3Y group ((20.19±1.53)s) and low dose GluA2-3Y group ((20.31±2.06)s) were longer than that in 2VO group( t=2.71, 2.35, both P<0.05). The discrimination coefficients in high dose GluA2-3Y group (0.47±0.10) and low dose GluA2-3Y group (0.59±0.06) were higher than that of 2VO group ( t=2.21, 3.94, both P<0.05). (2)The Western blot results showed that the expression of PSD-95 and GluA2 in hippocampus of rats in 2VO group were significantly lower than those in Sham group ( t=2.31, 2.20, both P<0.05), and the expression of PSD-95 in high dose GluA2-3Y group (1.026±0.056) was significantly higher than that in 2VO group ((0.760±0.061), t=2.49, P<0.05), while there was no significant difference between low-dose GluA2-3Y group and 2VO group( t=0.96, P>0.05). The expression of GluA2 in low-dose GluA2-3Y group was higher than that in 2VO Group ((1.130±0.087), (0.766±0.080), t=2.37, P<0.05), but there was no significant difference between high-dose GluA2-3Y group and 2VO group( t=1.06, P>0.05). (3) Immunofluorescence showed that compared with Sham group, the expression of PSD-95 and GluA2 in 2VO group decreased ( t=4.23, 2.57, P<0.05). Compared with 2VO group, the expression of PSD-95 and GluA2 in high dose GluA2-3Y group and low dose GluA2-3Y group increased significantly, and the differences were statistically significant (PSD-95: (7.757±0.578), (12.057±0.578), t=3.14, 6.96, both P<0.05; (9.721±0.950), (16.610±0.950), t=4.56, 9.34, both P<0.05). (4) The results of Western blot showed that the expression GSK3β in hippocampus of rats in each group were not statistically different( F=2.03, P>0.05). There were significant differences in the expression of Akt1, p-GSK3β and the percentage of p-GSK3β/GSK3β in hippocampus of rats in each group ( F=8.30, 4.76, 3.57, all P<0.05). Compared with Sham group, the levels of Akt1, p-GSK3β and the percentage of p-GSK3β/GSK3β in 2VO group were significantly lower ( t=3.00, 2.81, 3.17, all P<0.05). Compared with 2VO group, the levels of Akt1, p-GSK3β and p-GSK3β/GSK3β percentage in low dose GluA2-3Y group and high-dose GluA2-3Y group were significantly higher (Akt1: t=2.05, 5.20, both P<0.05; p-GSK3β: t=2.49, 4.15, both P<0.05; p-GSK3β/GSK3β percentage: t=2.30, 2.97, both P<0.05). Conclusion:GluA2-3Y, an AMPA receptor internalization inhibitor, can alleviate the cognitive impairment in rats with chronic cerebral hypoperfusion, which may be related to the increased expression of Akt1, p-GSK3β and postsynaptic proteins.