Guided by molecular networking, nine novel curvularin derivatives (1-9) and 16 known analogs (10-25) were isolated from the hydrothermal vent sediment fungus Penicillium sp. HL-50. Notably, compounds 5-7 represented a hybrid of curvularin and purine. The structures and absolute configurations of compounds 1-9 were elucidated via nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction, electronic circular dichroism (ECD) calculations, ¹³C NMR calculation, modified Mosher's method, and chemical derivatization. Investigation of anti-inflammatory activities revealed that compounds 7-9, 11, 12, 14, 15, and 18 exhibited significant suppressive effects against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in murine macrophage RAW264.7 cells, with IC₅₀ values ranging from 0.44 to 4.40 μmol·L^-1. Furthermore, these bioactive compounds were found to suppress the expression of inflammation-related proteins, including inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), NLR family pyrin domain-containing protein 3 (NLRP3), and nuclear factor kappa-B (NF-κB). Additional studies demonstrated that the novel compound 7 possessed potent anti-inflammatory activity by inhibiting the transcription of inflammation-related genes, downregulating the expression of inflammation-related proteins, and inhibiting the release of inflammatory cytokines, indicating its potential application in the treatment of inflammatory diseases.
Penicillium/chemistry* ; Mice ; Animals ; Anti-Inflammatory Agents/isolation & purification* ; RAW 264.7 Cells ; Nitric Oxide/metabolism* ; Hydrothermal Vents/microbiology* ; Macrophages/immunology* ; Molecular Structure ; Nitric Oxide Synthase Type II/immunology* ; Cyclooxygenase 2/immunology* ; Geologic Sediments/microbiology* ; NF-kappa B/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology*

Objective:To investigate the local hemodynamic spatial distribution of internal carotid artery stenosis and its correlation with plaque characteristics using high-resolution vessel wall imaging (HR-VWI) combined with computational fluid dynamics.Methods:This was a cross-sectional study. A retrospective analysis was conducted on the clinical and imaging data of 70 patients with moderate to severe stenosis at the initiation of the internal carotid artery in First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and Tianjin First Central Hospital from March 2018 to June 2020. All patients underwent HR-VWI and CT angiography examinations. The parameters related to plaque characteristics, such as plaque length, maximum wall thickness, plaque volume, wall volume percentage and intraplaque hemorrhage (IPH) were measured and evaluated on HR-VWI images. CT angiography images were used to construct a local hemodynamic vascular model to measure various wall shear stress (WSS) derived parameters, such as time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and transverse wall shear stress (transWSS), at the narrowest, proximal, and distal parts of the lesion. The Friedman test was used to analyze the difference of hemodynamic parameters in different parts of the lesion. Spearman correlation analysis was performed to assess the correlation between plaque burden and local hemodynamic parameters. Univariate and multivariate logistic regression analyses were used to explore the independent risk factors for predicting IPH.Results:Among the 70 patients, 25 patients with IPH and 45 patients without IPH. The overall differences in TAWSS, OSI, RRT and transWSS at the narrowest, proximal, and distal parts of the lesion in 70 patients were statistically significant ( P<0.05). The TAWSS and transWSS at the narrowest parts were significantly higher than those at the proximal and distal parts ( P<0.05). The OSI at the distal part was significantly higher than that at the narrowest and the proximal parts ( P<0.05). The RRT at the proximal part was significantly lower than that at the narrowest and the distal parts ( P<0.05). Spearman correlation analysis showed RRT at the distal part was correlated with plaque volume ( r s=0.249, P=0.044) and wall volume percentage ( r s=0.286, P=0.016), respectively. In a multivariate logistic regression showed plaque length ( OR=1.315, 95% CI 1.073-1.612, P=0.008) and TAWSS at the narrowest part ( OR=1.631, 95% CI 1.308-1.854, P=0.008) were independent risk factors for predicting IPH. Conclusions:The spatial distribution of local hemodynamics of moderate to severe stenosis at the initiation of the internal carotid artery is different, and the WSS parameters in different parts of the lesion have different effects on plaque volume, wall volume percentage and IPH.

Objective To provide ideas and reference for the anti-infective drug treatment and pharmaceutical care of brain abscess caused by Nocardia brasiliensis.Methods Clinical pharmacists participated in the treatment of a patient with brain abscess caused by Nocardia brasiliensis.According to the patient's medical history,clinical symptoms,and test results,clinical pharmacists refer to the guidelines assisted physician to formulate the anti-infection treatment scheme of trimethoprim-sulfamethoxazole(SMZ-TMP)combined with imipenem/cilastatin and amikacin,and the pharmaceutical care.The dosage of amikacin was adjusted through therapeutic drug monitoring(TDM),and promptly identified adverse reactions such as myelosuppression caused by linezolid and SMZ-TMP.Results The physician adopted the pharmacist's suggestion,and the patient was discharged after treatment.Conclusion The anti-infection regimen for brain abscess caused by Nocardia brasiliensis depends on the drug sensitivity data of Nocardia,the severity of infection,the immune state of the host,and the PK/PD characteristics and adverse reactions of antibiotics.By participating in the pharmaceutical care of brain abscess caused by Nocardia brasiliensis,clinical pharmacists assisted physicians in optimizing drug treatment plans,ensuring the safety and effectiveness of clinical medication.

Objective To provide ideas and reference for the anti-infective drug treatment and pharmaceutical care of brain abscess caused by Nocardia brasiliensis.Methods Clinical pharmacists participated in the treatment of a patient with brain abscess caused by Nocardia brasiliensis.According to the patient's medical history,clinical symptoms,and test results,clinical pharmacists refer to the guidelines assisted physician to formulate the anti-infection treatment scheme of trimethoprim-sulfamethoxazole(SMZ-TMP)combined with imipenem/cilastatin and amikacin,and the pharmaceutical care.The dosage of amikacin was adjusted through therapeutic drug monitoring(TDM),and promptly identified adverse reactions such as myelosuppression caused by linezolid and SMZ-TMP.Results The physician adopted the pharmacist's suggestion,and the patient was discharged after treatment.Conclusion The anti-infection regimen for brain abscess caused by Nocardia brasiliensis depends on the drug sensitivity data of Nocardia,the severity of infection,the immune state of the host,and the PK/PD characteristics and adverse reactions of antibiotics.By participating in the pharmaceutical care of brain abscess caused by Nocardia brasiliensis,clinical pharmacists assisted physicians in optimizing drug treatment plans,ensuring the safety and effectiveness of clinical medication.

Objective:To investigate the local hemodynamic spatial distribution of internal carotid artery stenosis and its correlation with plaque characteristics using high-resolution vessel wall imaging (HR-VWI) combined with computational fluid dynamics.Methods:This was a cross-sectional study. A retrospective analysis was conducted on the clinical and imaging data of 70 patients with moderate to severe stenosis at the initiation of the internal carotid artery in First Teaching Hospital of Tianjin University of Traditional Chinese Medicine and Tianjin First Central Hospital from March 2018 to June 2020. All patients underwent HR-VWI and CT angiography examinations. The parameters related to plaque characteristics, such as plaque length, maximum wall thickness, plaque volume, wall volume percentage and intraplaque hemorrhage (IPH) were measured and evaluated on HR-VWI images. CT angiography images were used to construct a local hemodynamic vascular model to measure various wall shear stress (WSS) derived parameters, such as time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), and transverse wall shear stress (transWSS), at the narrowest, proximal, and distal parts of the lesion. The Friedman test was used to analyze the difference of hemodynamic parameters in different parts of the lesion. Spearman correlation analysis was performed to assess the correlation between plaque burden and local hemodynamic parameters. Univariate and multivariate logistic regression analyses were used to explore the independent risk factors for predicting IPH.Results:Among the 70 patients, 25 patients with IPH and 45 patients without IPH. The overall differences in TAWSS, OSI, RRT and transWSS at the narrowest, proximal, and distal parts of the lesion in 70 patients were statistically significant ( P<0.05). The TAWSS and transWSS at the narrowest parts were significantly higher than those at the proximal and distal parts ( P<0.05). The OSI at the distal part was significantly higher than that at the narrowest and the proximal parts ( P<0.05). The RRT at the proximal part was significantly lower than that at the narrowest and the distal parts ( P<0.05). Spearman correlation analysis showed RRT at the distal part was correlated with plaque volume ( r s=0.249, P=0.044) and wall volume percentage ( r s=0.286, P=0.016), respectively. In a multivariate logistic regression showed plaque length ( OR=1.315, 95% CI 1.073-1.612, P=0.008) and TAWSS at the narrowest part ( OR=1.631, 95% CI 1.308-1.854, P=0.008) were independent risk factors for predicting IPH. Conclusions:The spatial distribution of local hemodynamics of moderate to severe stenosis at the initiation of the internal carotid artery is different, and the WSS parameters in different parts of the lesion have different effects on plaque volume, wall volume percentage and IPH.

Objective:To systematically integrate qualitative researches on the financial toxicity experience of cancer patients, so as to provide reference for formulating intervention strategies for financial toxicity in cancer patients.Methods:Qualitative studies on financial toxicity experience of cancer patients were searched in Web of Science, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP, Wanfang data, and China Biology Medicine disc, with a search period from database establishment to August 31, 2023. The quality of the included literature was evaluated using the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence Based Health Care Center in Australia. The aggregation integration method was used to integrate the results.Results:A total of 12 articles were included, and 68 research results were extracted and categorized into 15 new categories. Four integrated results were obtained, including anxiety and stress under financial difficulties, relying on family members to start a new in adversity, and dancing together with treatment and life to write a new article, and great expectations for the future.Conclusions:Pay attention to the financial toxicity of cancer patients, actively seek response strategies, and bring benefits to cancer patients.

To summarize the perioperative nursing experience of a child with Berry syndrome who underwent radical surgery.The key points of preoperative care include the prevention of heart failure and vigilance against ischemia and hypoxia in the lower limbs.The key points of postoperative care include maintaining stable cardiac function,preventing pulmonary hypertension crisis,ensuring safe transition during delayed chest closure,paying attention to psychological support,and emphasizing continuous care.After 54 days of careful treatment and nursing care,the child recovered well and was discharged from the hospital.The follow-up was couducted a month after discharge,and the child was good.

Objective:To explore the effect of dynamic changes of cerebral oxygen saturation before and after treatment on the progression of infarction in patients with acute ischemic stroke (AIS).Methods:Totally 39 patients with first onset AIS within 24 hours in Tianjin First Central Hospital and Shanghai Fourth People′s Hospital Affiliated to Tongji University from May 2018 to July 2020 were enrolled retrospectively. All patients underwent multi-modal MR at admission (baseline) and within 2 weeks after standardized treatment, including diffusion weighted imaging (DWI), susceptibility weighted imaging (SWI), and dynamic magnetic sensitive contrast-enhanced magnetic resonance perfusion imaging (DSC-PWI). The degree of asymmetrically prominent cortical vein (APCV) at admission was observed on SWI, and the venous oxygen saturation (SvO 2) of APCV on the infarcted cerebral hemisphere was calculated in all patients before and after treatment. The original DWI and DSC-PWI images obtained from two MR scans were imported into the software to obtain the delayed perfusion volume [peak time (T max)>6 s] and the infarct core volume (apparent diffusion coeffivient value<620×10 -6 mm 2/s). According to the comparison of baseline infarct core (DWI-ASPECT) score and follow-up (FUP-ASPECT) score, all patients were divided into infarct progression group (27 cases) and non-infarct progression group (12 cases). Two independent sample t-test or Mann Whitney U-test were used to compare the differences of baseline infarct core volume, baseline SvO 2, SvO 2 change, baseline hypoperfusion volume and hypoperfusion volume change between the two groups. Univariate analysis and multivariate logistic regression analysis were used to obtain independent predictors of infarct progression. Pearson correlation analysis was used to evaluate the correlation between SvO 2 change, hypoperfusion volume change and infarct change score respectively. Results:Difference in baseline infarct core volume, baseline SvO 2, hypoperfusion volume and hypoperfusion volume change between infarct progression group and non-progression group had no statistical significance ( P>0.05). There was significant difference in the change of SvO 2 between the infarct progression group and non-infarct progression group after treatment [(27±11)%, (35±6)% respectively, t=-2.56, P=0.015]. Univariate logistic regression analysis showed that the change value of SvO 2 was the influencing factor of infarction progression of AIS (OR=0.872, 95%CI 0.773-0.984, P=0.026). Multivariate logistic regression analysis showed that the baseline NIHSS score (OR=1.248, 95%CI 1.042-1.494, P=0.016) was an independent predictor of infarction progression in AIS, and the change value of SvO 2 (OR=0.814, 95%CI 0.688-0.964, P=0.017) was an independent protective factor. The change of SvO 2 was positively correlated with the score of infarct change ( r=0.425, P=0.007). Conclusions:The change of SvO 2 after AIS treatment can independently predict the progress of acute infarction. Improvement of SvO 2 after treatment is conducive to delay the progress of infarction.

Objective:To investigate the feasibility of predicting lateral cervical lymph node metastasis (LLNM) in patients with papillary thyroid carcinoma (PTC) based on the nomogram constructed by dual-energy CT data.Methods:In total 417 patients with PTC confirmed by pathology in Tianjin First Central Hospital from January 2015 to December 2018 were retrospectively analyzed as a training group. Internal validation was conducted, including 139 patients in the LLNM group and 278 patients in the non-LLNM group. A total of 169 PTC patients from January 2019 to June 2020 were included as an external validation group, including 58 patients in the LLNM group and 111 patients in the non-LLNM group. The morphological characteristics of the primary thyroid lesions on dual-energy CT iodine maps were analyzed, including tumor location, maximum diameter, calcification, and extrathyroidal extension (ETE). Iodine concentration (IC) of the PTC parenchyma and the internal carotid artery on the same level in the arterial and venous phases were measured, and normalized iodine concentration (NIC) was calculated. The independent risk factors for LLNM were obtained by univariate and multivariate logistic regression analysis. Base on the results, a prediction model was constructed and expressed in the form of a nomogram. The internal and external validation of the model was carried out using ROC curve.Results:Multivariate binary logistic regression analysis showed that the lesion location in the upper polar of the thyroid, the presence of ETE, IC in arterial phase>2.9 mg/ml, IC in the venous phase>3.2 mg/ml, and NIC in the arterial phase>0.21 were independent risk factors for LLNM prediction. The nomogram based on the above factors was constructed with an area under the ROC curve (AUC) of 0.895 (95%CI 0.862-0.923). With a cut-off value of 0.79, the sensitivity and specificity were 86.3% and 75.2%, respectively. As for the external validation group, the AUC of the model was 0.887 (95%CI 0.830-0.931), with the sensitivity of 82.8%, and the specificity of 81.1%.Conclusion:The application values of the nomogram model based on dual-energy CT data in preoperative evaluation of the possibility of LLNM of PTC patients has been verified. The model constructed in this study might be helpful with the individualized treatment in a certain degree.

Objective To investigate the clinical efficacy and safety of wedge osteotomy combined with internal fixation for ulnar olecranon fracture of Mayo type ⅡB.Methods From July 2014 to December 2017,8 patients with ulnar olecranon fracture of Mayo type ⅡB were treated with wedge osteotomy of the ulnar olecranon combined with internal fixation.They were 6 men and 2 women,from 28 to 45 years of age (mean,31.4 years).The wedge osteotomy was planned preoperatively according to the literature data and the osteotomy lengths were measured postoperatively to confirm the safe range for the surgery.Fracture healing was evaluated by regular X-ray follow-up and therapeutic effects were assessed by the range of elbow motion and the Broberg-Morry scoring system.Results On average in this group,the olecranon osteotomy was 6.2 mm in length on the articular sudace and 14.5 mm at the basal part.The olecranon was shortened by 4.6 cm on average after operation.All the 8 patients were followed up for 14 to 20 months (average,16.4 months).The clinical fracture healing time ranged from 12 to 16 weeks,with an average of 14.3 weeks.Follow-ups revealed no fracture displacement,pain or internal fixation failure.No significant differences were found between the affected and the contralateral sides in the flexion,extension or range of motion of the elbow joint at 3 months or at one year after surgery (P ＞ 0.05).According to the Broberg-Morry scoring system,5 cases were rated as excellent,2 as good and one as fair at 3 months after surgery.The final follow-ups found no traumatic arthritis or joint instability.Conclusions As a new treatment alternative,wedge osteotomy combined with internal fixation can obtain satisfactory curative outcomes for ulnar olecranon fractures of Mayo type ⅡB.The wedge osteotomy was performed in a safe range for this group.