A chemical investigation of secondary metabolites (SMs) from Aspergillus nidulans resulted in the identification of five novel dioxopiperazine (DKP)-diphenyl ether hybrids, designated as diphenylemestrins A-E (1-5). These compounds 1-5 represent the first known dimers combining DKP and diphenyl ether structures, with compound 4 featuring an uncommon dibenzofuran as the diphenyl ether component. The structural elucidation and determination of absolute stereochemistry were accomplished through spectroscopic analysis and electronic circular dichroism (ECD) calculations. Notably, diphenylemestrin C (3) exhibited moderate cytostatic activity against NB4 cells, with a half maximal inhibitory concentration (IC₅₀) value of 21.99 μmol·L^-1, and induced apoptosis at higher concentrations.
Aspergillus nidulans/metabolism* ; Diketopiperazines/pharmacology* ; Molecular Structure ; Phenyl Ethers/pharmacology* ; Humans ; Apoptosis/drug effects* ; Cell Line, Tumor

Objectives:This study aims to investigate the impact of different Low-Density Lipoprotein cholesterol(LDL-C)levels on progression of intermediate coronary stenosis,and the associated risk factors leading to the progression of such lesions. Methods:Data were collected on 219 consecutive patients admitted at the Fuwai Central China Vascular Hospital from January 2020 to February 2021,underwent angiographic examinations and diagnosed with intermediate coronary stenosis,with at least one follow-up angiography after 11 months.Offline quantitative flow ratio(QFR)analysis was performed on these cases.Patients were divided into two groups:LDL-C controlled group(LDL-C<1.8 mmol/L,148 patients with 191 vessels)and LDL-C uncontrolled group(LDL-C≥1.8 mmol/L,71 patients with 98 vessels).Coronary artery QFR and anatomical indicators such as minimal lumen diameter,minimal lumen area,percentage diameter stenosis,percentage area stenosis were compared within and between the groups.Further analysis was performed to identify influencing factors leading to changes in coronary physiological parameters derived from QFR. Results:Within the LDL-C controlled group,there was no significant difference in the QFR values of the vessels compared to baseline(P>0.05),whereas in the LDL-C uncontrolled group(P<0.05),a notable decline in QFR was observed.Patients in the LDL-C controlled group had lower rates of maximum diameter and area stenosis and higher minimum lumen diameter and area(all P<0.05).Through multifactorial Logistic regression analysis,it was found that a body mass index＞28 kg/m2,LDL-C≥1.8 mmol/L,and a history of myocardial infarction were independent risk factors leading to the decline in QFR(all P<0.05). Conclusions:It was found that patients in the LDL-C controlled group had higher coronary artery QFR,minimum lumen diameter and area,lower rates of maximum diameter and area stenosis.

Objective:To study the emergency cerebral hemorrhage grading scale (EDICH) score and the modified emergency intracerebral hemorrhage grading scale (mEDICH) score on the adverse prognosis of patients with cerebral hemorrhage 90 days after discharge.Methods:The clinical data of 248 patients with cerebral hemorrhage in the Department of Neurosurgery, Lianyungang Hospital Affiliated to Xuzhou Medical University from January 2022 to December 2022 were retrospectively analyzed. According to the modified Rankin scale (mRS) 90 days after discharge, patients were divided into a good prognosis group (212 cases) and a poor prognosis group (36 cases). Independent-samples t-test and rank-sum test were used to compare the basic information, vital signs, laboratory tests, imaging characteristics, EDICH score and mEDICH score of the two groups. Multivariate Logistic regression was used to analyze the risk factors affecting the poor prognosis of patients with cerebral hemorrhage. The receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of EDICH score and mEDICH score for the poor prognosis of patients with intracerebral hemorrhage 90 days after discharge.Results:The diameter of intracerebral hematoma (5.53±0.32) cm, the rate of intraventricular hemorrhage (61.11%,22/36) and the rate of subtentorial hemorrhage (27.78%, 10/36) in poor prognosis group were significantly higher than those in good prognosis group (3.50±0.07) cm, intraventricular hemorrhage (30.19%, 64/212) and infratentorial hemorrhage (14.15%, 30/212), the differences were statistically significant ( t=6.19, P<0.001; χ 2=12.99, P<0.001; χ 2=4.22, P=0.040). GCS scores in the poor prognosis group were lower than those in the good prognosis group ( H=72.01, P<0.001). EDICH scores and mEDICH scores in the poor prognosis group were higher than those in the good prognosis group (EDICH score: H=65.79, P<0.001; mEDICH score: H=76.56, P<0.001). Multivariate Logistic regression analysis showed EDICH score ( OR=5.869,95% CI 3.451-9.981, P<0.05) and mEDICH score ( OR=10.353,95% CI 4.842-22.137, P<0.05)could predict the prognosis of patients with cerebral hemorrhage 90 days after discharge. ROC curve analysis showed that the sensitivity and specificity of EDICH score and mEDICH score were 0. 861,0.889 and 0. 821,0.953, respectively, but the predictive effect of mEDICH score was significantly better than that of EDICH score ( Kappa values were 0. 787 and 0. 494, respectively). The predicted results are highly consistent with the actual results. Conclusion:MEDICH score can accurately predict the prognosis of patients with intracerebral hemorrhage 90 days after discharge, which has clinical application value.

Objective:To investigate the treatment and prognosis of acute carotid artery occlusion during perioperative period of carotid endarterectomy (CEA).Methods:The clinical data of 112 carotid artery stenosis patients who underwent CEA from January 2017 to December 2021 in Lianyungang Hospital Affiliated to Xuzhou Medical University were retrospectively analyzed. The patients were followed up at 6 to 9 months after surgery, the clinical prognosis was evaluated by Glasgow outcome score (GOS), and the head and neck CT angiography (CTA) was performed.Results:Among the 112 patients, 5 patients underwent acute carotid artery occlusion during the perioperative period, including 1 case of intraoperative acute occlusion of internal carotid artery and 1 case of intraoperative internal carotid artery combined with external carotid artery cute occlusion, both of them were re-sutured, and multi-mode monitoring showed that each carotid artery was unobstructed; 2 cases of intraoperative external carotid artery occlusion, no re-suture was performed during the operation; 1 case of intraoperative monitoring showed no obvious abnormality, and the contralateral limb hemiplegia was observed after surgery, and the muscle strength was grade 1, the carotid color Doppler ultrasound showed the occlusion of the internal carotid artery on the operation side. The CT and CTA examination showed focal infarction and common carotid artery on the operation side, and drugs and conservative treatment were given. The follow-up result: GOS 5 scores was in 4 cases, and 4 scores in 1 case; the muscle strength of hemiplegia patient recovered to grade 4; head and neck CTA examination, except for 1 case of common arterial occlusion, the other 4 cases showed no special abnormality.Conclusions:Intraoperative acute carotid artery occlusion can be detected timely by intraoperative multi-mode hemodynamic monitoring during CEA. Vascular recanalization after acute occlusion is possible by adopting active and effective treatment methods, the occurrence of postoperative ischemic stroke can be effectively prevented and the prognosis of patients can be improved.

Objective:To investigate the effects of exogenous hydrogen sulfide on myocardial fibrosis and apoptosis in rats after myocardial infarction and the underlying mechanisms.Methods:Forty-three Sprague Dawley(SD)rats were divided into 4 groups according to the random number table method: a control group(n=12), a myocardial infarction group(MI group, n=13), an hydrogen sulfide(H 2S)group(n=6)and an MI+ H 2S group(n=12). The rat model of acute myocardial infarction was established by intraperitoneal injections of isoproterenol(50 mg/kg, once a day, for 2 days). Electrocardiogram and troponin changes were recorded 48 h after the last drug administration to determine whether the rat model was successfully constructed.After successful establishment of the model, rats in the MI group and the MI+ H 2S group were intraperitoneally injected with sodium hydrosulfide(56 μmol/kg, once a day, for 6 weeks).6 weeks later, echocardiogram and Masson's trichrome staining were performed to assess changes in cardiac function and collagen volume fraction in each group.Terminal deoxynucleotidyl transferase(TdT)dUTP nick end labeling(TUNEL)was used to detect the myocardial apoptosis rate in each group, and Western-blot was used to detect protein expression of Yes-related protein 1(YAP1), WW domain containing transcriptional regulator1(TAZ), mammalian Ste20-like kinase 2(MST2), Bcl-2-associated X protein(Bax), cysteine protease 3(caspase-3), the ratio of matrix metalloproteinase 3(MMP3)/matrix metalloproteinase inhibitor 2(TIMP2), and B-cell lymphoma factor(Bcl-2). Results:Compared with the control group, myocardial collagen volume fraction was increased( P<0.05), the myocardial cell apoptosis rate was increased( P<0.05), and myocardial YAP1, TAZ, MST2, Bax, caspase-3 protein expression and MMP3/TIMP2 ratio were increased in the MI group(all P<0.05), while the expression of Bcl-2 protein was decreased( P<0.05). Compared with the MI group, collagen volume fraction and the cardiomyocyte apoptosis rate were significantly decreased in the MI+ H 2S group( P<0.05). Also, protein expression of YAP1(2.406±0.024 vs.2.830±0.063), TAZ(0.964±0.090 vs.1.329±0.018), MST2(0.780±0.082 vs.1.788±0.097), Bax(1.500±0.008 vs.0.613±0.003)and caspase-3(0.620±0.024 vs.0.780±0.012)and the MMP3/TIMP2 ratio were decreased(all P<0.05), while protein expression of Bcl-2 was increased( P<0.05)in myocardial tissue. Conclusions:H 2S can mitigate myocardial fibrosis after myocardial infarction, through inhibiting the activation of the YAP1/TAZ signaling pathway, thus reducing apoptosis of cardiomyocytes.

Psychological research results confirmed that the negative impact of shame on self often causes psychological diseases, and shame does not always related to ethical value. People with serious sense of shame will lead to negative evaluation and overall negation to themselves, and the sense of shame accompanied by great pain will cause great harm to individuals. To realize the sublimation of shame, the ethical orientation of its self cognitive schema and evaluation method must be changed, from the orientation of "transforming self and reaching perfection" to the position of "caring for self and accepting imperfect self" . To tap the positive value of shame, individuals must avoid hurting themselves and then care for themselves. "The principle of not harming life" and "do not denying people’s ethical subject status" are the bottom line of the ethical value of shame.

OBJECTIVE To identify an d analyze chemical cons tituents of Pleione yunnanensis with origin of Pleione yunnanensis. METHODS UPLC-Q-Exactive-Plus-Orbitrap-MS was adopted. The determination was performed on Hyperdil GOLD column with mobile phase consisted of 0.1％ formic acid solution-0.1％ formic acid acetonitrile solution （gradient elution ）at the flow rate of 0.3 mL/min. The column temperature was set at 40 ℃，and sample size was 2 µL. The electrospray ion source was adopted，and the scanning range was m/z 100-1 500，and the scanning mode was positive and negative ion exchange mode of full scan+ddMS2. The structure of chemical constituents were determined by using Compound Discoverer 3.1 software，comparing with mzCloud，PubChem network database and OTCML ，on the basis of reference substance and published literatures. RESULTS & CONCLUSIONS A total of 42 chemical constituents were identified （positive ion mode has 24，negative ion mode has 27）， including 13 benzyl succinate glycosides （such as dactylorhin C ，coelovirin A ，militarine），4 phenol glycosides （such as adenosine ， guanosine，gastrodin），3 alkaloids（choline，betaine，berberine），and one flavonoid （nobiletin），7 aromatics（such as DL-lysine ， DL-arginine，DL-glutamine），one sugar （sucrose），3 benzenes（shancigusin H ，shancigusin H isomer ，batatasin Ⅲ）and 10 others （such as p-methoxybenzoic acid ，monomethyl dodecanedioate ，diphenylamine）. Glucose oxybenzyl and some small mole cules are easy to be lost in the cleavage of benzyl succinate glycosides；glycosyl is easy to be lost in the cleavage of phenol glycosides；the cleavage of alkaloids mainly manifest as the cleavage and loss of small molecular substituents ；demethyla- tion reaction is occurred in most flavonoids.

【Objective】 To analyze the data of non-small cell lung cancer (NSCLC) gene chip using the bioinformatics method, screen differential expression genes (DEGs), and explore the biomarkers related to the prognosis of NSCLC so as to provide a new target for the treatment of NSCLC. 【Methods】 The NSCLC gene chip data were downloaded from the GEO database and the common DEGs in the two datasets were screened by GEO2R tool and FunRich3.1.3 software. The DAVID database was used in GO analysis and KEGG analysis of the DEGs. The protein-protein interaction (PPI) network was constructed using the STRING database; Cytoscape 3.8.0 software was used to select the top 20 hub genes. Then Kaplan-Meier plotter was used to analyze the prognosis of the identified hub genes, and multiple external databases were used to verify the expressions of the hub genes and their relationship with prognosis. 【Results】 A total of 159 intersect DEGs were screened from the two datasets. A total of 20 hub genes were identified via PPI network. Survival analysis and validation results from multiple external databases showed that SPP1 was highly expressed in NSCLC tumor tissues and was significantly correlated with the patients’ poor prognosis (P<0.05). The subgroup analysis showed that SPP1 might cause the poor prognosis by affecting lymph node metastasis. 【Conclusion】 SPP1 may be a biomarker for evaluating the prognosis of NSCLC patients, providing a new idea for the targeted therapy of NSCLC.

Objective:To evaluate the value of p16 INK4a detected by p16 INK4a immunostaining as a new generation of cervical cytology for primary screening and secondary screening in population-based cervical cancer screening, and in improving cytological diagnosis. Methods:Between 2016 and 2018, 5 747 non-pregnant women aged 25-65 years with sexual history were recruited and underwent cervical cancer screening via high-risk (HR)-HPV/liquid-based cytological test (LCT) test in Shenzhen and surrounding areas. All slides were immuno-stained using p16 INK4a technology, among them, 902 cases were offered p16 INK4a detection during primary screening, and the remaining 4 845 cases were called-back by the virtue of abnormal HR-HPV and LCT results for p16 INK4a staining. Participants with complete LCT examination, HR-HPV test, p16 INK4a staining and histopathological examination results were included in this study. The performance of p16 INK4a in primary and secondary screening, and in assisting cytology to detect high grade squamous intraepithelial lesion [HSIL, including cervical intraepithelial neoplasia (CIN) Ⅱ or Ⅲ] or worse [HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) +] were analyzed. Results:(1) One-thousand and ninety-seven cases with complete data of p16 INK4a and histology were included. Pathological diagnosis: 995 cases of normal cervix, 37 cases of low grade squamous intraepithelial lesion (LSIL), 64 cases of HSIL and one case of cervical cancer were found. Among them, 65 cases of HSIL (CIN Ⅱ) + and 34 cases of HSIL (CIN Ⅲ) + were detected. The positive rate of p16 INK4a in HSIL (CIN Ⅱ) + was higher than that in CINⅠ or normal pathology (89.2% vs 10.2%; P<0.01). (2) p16 INK4a as primary screening for HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) + was equally sensitive to primary HR-HPV screening (89.2% vs 95.4%, 94.1% vs 94.1%; P>0.05), but more specific than HR-HPV screening (89.8% vs 82.5%, 87.7% vs 80.2%; P<0.05). p16 INK4a was equally sensitive and similarly specific to cytology (≥LSIL; P>0.05). (3) The specificity of LCT adjunctive p16 INK4a for detecting HSIL (CIN Ⅱ) + or HSIL (CIN Ⅲ) + were higher than that of LCT alone or adjunctive HR-HPV ( P<0.01), while the sensitivity were similar ( P>0.05). (4) p16 INK4a staining as secondary screening: p16 INK4a was significantly more specific (94.1% vs 89.7%, 91.9% vs 87.4%; P<0.01) and comparably sensitive (84.6% vs 90.8%, 88.2% vs 91.2%; P>0.05) to cytology for triaging primary HR-HPV screening. HPV 16/18 to colposcopy and triage other HR-HPV with p16 INK4a was equally sensitive (88.2% vs 94.1%; P=0.500) and more specific (88.3% vs 83.0%; P<0.01) than HPV 16/18 to colposcopy and triage other HR-HPV with LCT≥ atypical squamous cells of undetermined significance (ASCUS), and the referral rate decreased (14.0% vs 19.4%; P=0.005). Conclusions:For primary screening, p16 INK4a is equally specific to cytology and equally sensitive to HR-HPV screening. p16 INK4a alone could be an efficient triage after primary HR-HPV screening. In addition, p16 INK4a immunostaining could be used as an ancillary tool to cervical cytological diagnosis, and improves its accuracy in cervical cancer screening.

OBJECTIVE：To provide reference for improving the quality standard of Rhizoma Bego niae from Guizhou . METHODS：Five batches of Rhizoma Begoniae from Guizhou were collected ，and the microscopic characteri stics of the Rhizoma Begoniae powder were observed. According to the corresponding methods in 2015 edition of Chinese Pharmacopoeia （part Ⅳ）， potent adenosine 50-triphosphate competitive phosphati - dylinositol-3-kinase/mammalian target of rapamycin inhibitors：discovery of compound 26（PKI-587），a highly effi cacious dual inhibitor Morpholine as a privileged structure ：a review on the me - dicinal chemistry and pharmacological activity of morpho - line containing bioactive molecules[J]. Med Res Rev ， qq.com 2019. DOI ：10.1002/med.21634. qualitative identification of Rhizoma Begoniae was conducted by TLC ，and the contents of moisture ，total ash and water-soluble extract in Rhizoma Begoniae were determined. The contents of rutin were determined by HPLC. RESULTS ：The powder of Rhizoma Begoniae medicinal materials was brown ，stone cells were square ，polygonal-like or irregular. There were many starch grains and few complex grains. The conduit ，calcium oxalate square crystal/cluster crystal were visible. The same fluorescence spots were found in the same location of TLC atlas of Rhizoma Begoniae control herb. The moisture ，total ash ，water-soluble extract contents were 10.15％-11.41％，8.70％-12.59％ and 16.91％-19.58％，respectively. The linear range of rutin were 18.47-147.8 μg/mL （r＝0.999 8）；RSDs of reproducibility ，intermediate precision and stability tests （8 h）were all lower than 3.0％；the average recoveries were 99.39％-100.29％（RSDs were 0.23％-2.59％，n＝3）；the contents of rutin in 5 batches of Rhizoma Begoniae were 0.102％-0.198％. CONCLUSIONS ：The contents of moisture and total ash shall not exceed 13.0％ and 14.0％ respectively， and the contents of water-soluble extract and rutin shall not be less than 15.0％ and 0.080％. The quality standard established in this study can be used for the quality control of Rhizoma Begoniae from Guizhou.