Cancer represents a significant disease that profoundly impacts human health and longevity. Projections indicate a 47% increase in the global cancer burden by 2040 compared to 2020, accompanied by a further rise in the associated economic burden. Consequently, there is an urgent need to discover and develop new alternative drugs to mitigate the global impact of cancer. Natural products (NPs) play a crucial role in the identification and development of anticancer therapeutics. This study identified ustusolate E (UE) and its analog 11α-hydroxy-ustusolate E (HUE) from strain Aspergilluscalidoustus TJ403-EL05, and examined their antitumor activities and mechanisms of action. The findings demonstrate that both compounds significantly inhibited the proliferation and colony formation of AGS (human gastric cancer cells) and 786-O (human renal clear cell carcinoma cells), induced irreversible DNA damage, blocked the cell cycle at the G₂/M phase, and further induced apoptosis in tumor cells. To the best of the authors' knowledge, this is the first report on the anticancer effects of UE and HUE and their underlying mechanisms. The present study suggests that HUE and UE could serve as lead compounds for the development of novel anticancer drugs.
Humans ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Line, Tumor ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Tumor Suppressor Protein p53/genetics* ; Cell Proliferation/drug effects* ; Antineoplastic Agents/pharmacology* ; Sesquiterpenes/pharmacology* ; Aspergillus/chemistry*

Five novel nor-eremophilane-type sesquiterpenoids, peniroqueforins E-H and J (1-4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), along with four known compounds (6 and 10-12), were isolated and characterized from fungus Penicillium roqueforti (P. roqueforti). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC₅₀) value of paclitaxel (PTX) combined with 1 in SW620/Ad300 cells was 50.36 nmol·L^-1, which was 65-fold more potent than PTX alone (IC₅₀ 3.26 μmol·L^-1). Subsequent molecular docking studies revealed an affinity between compound 1 and P-glycoprotein (P-gp), suggesting that this nor-eremophilane-type sesquiterpenoid (1) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.
Penicillium/chemistry* ; Humans ; Sesquiterpenes/isolation & purification* ; Cell Line, Tumor ; Molecular Structure ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/pharmacology* ; Drug Resistance, Multiple/drug effects* ; Molecular Docking Simulation

Objective:To observe the change of retinal artery angle in eyes with idiopathic epiretinal membrane (ERM) and to analyze the relationship between retinal artery angle, ERM classification based on optical coherence tomography (OCT), and visual acuity.Methods:A retrospective cross-sectional clinical study. A total of 187 eyes in 187 patients diagnosed with monocular idiopathic ERM (IERM group) in Department of Ophthalmology of Zhejiang Provincial People's Hospital and the Affiliated Eye Hospital of Wenzhou Medical University at Hangzhou from November 2018 to January 2023 were included in the study. The contralateral healthy eyes were included as the control group. All patients underwent best corrected visual acuity (BCVA), fundus photography, spectral-domain OCT, OCT angiography (OCTA) and axial length (AL) measurement. BCVA examination was performed using the standard logarithmic visual acuity chart, which was converted to the logarithm of the minimum angle of resolution (logMAR) visual acuity. The foveal avascular zone (FAZ) area was measured by OCTA. The central macular thickness (CMT) was measured by spectral domain OCTaccording to the grading criteria of ectopic inner foveal layer (EIFL) was divided into stages 1 to 4 with 42, 45, 62, and 38 eyes, and the IERM group was subdivided into stage 1, stage 2, stage 3, and stage 4 groups accordingly. Image J was used to measure the retinal artery angle and the 1/2 retinal artery angle on fundus images. Multiple linear regression analysis was used to analyze the correlation between BCVA and artery angle, 1/2 artery Angle, CMT, FAZ area and AL.Results:Compared with the control group, eyes in IERM group had worse BCVA ( t=9.727), thicker CMT ( t=12.452), smaller FAZ area ( t=-14.329), smaller artery angle ( t=-9.165) and smaller 1/2 artery angle ( t=-9.549). The differences were statistically significant ( P<0.001). With the increase of IERM stage, the artery angle and 1/2 artery angle decreased significantly ( F=21.763, 12.515; P<0.001). There was no significant difference in artery angle and 1/2 artery angle between stage 1 group and stage 2 group, and 1/2 arterial angle between stage 2 group and stage 3 group ( P>0.05). There were significant differences in artery angle and 1/2 artery angle between the other groups ( P<0.05). There were significant differences in CMT and logMAR BCVA among different classification subgroups in IERM groups ( P<0.05). There was no significant difference in FAZ area between grade 3 group and grade 4 group ( P>0.05). There were significant differences in FAZ area between the other groups ( P<0.05). Correlation analysis showed that decreased artery angle ( P=0.013) and increased CMT ( P<0.001) were associated with decreased BCVA. Conclusions:Compared with healthy eyes, the artery angle decreases significantly with the increase of ERM stage. Decreased retinal artery angle is associated with decreased visual acuity in IERM eyes.

Objective To investigate the changes and clinical significance of serum pro-gastrin-releasing peptide (ProGRP), squamous cell carcinoma-related antigen (SCC), and carbohydrate antigen 72-4 (CA72-4) levels in patients with gastric cancer. Methods A total of 68 patients with gastric cancer (gastric cancer group), 37 patients with benign gastric lesions (benign gastric lesion group), and 30 healthy subjects (non-gastric disease group) were selected as the study participants. Serum ProGRP, SCC, and CA72-4 levels were compared among the three groups on admission. The relationships of serum ProGRP, SCC, and CA72-4 levels with pathological parameters were analyzed in the gastric cancer group. Patients in the gastric cancer group were followed up for 24-month after discharge. Multivariate Logistic regression analysis was used to identify the influencing factors of prognosis in gastric cancer patients. Receiver operating characteristic (ROC) curves were plotted and the area under the curve (AUC) was calculated to analyze the predictive value of serum ProGRP, SCC, and CA72-4 for death during follow-up in gastric cancer patients. Results The serum levels of ProGRP, SCC, and CA72-4 in the gastric cancer group were higher than those in the benign gastric lesion group and the non-gastric disease group, and the serum levels of ProGRP and CA72-4 in the benign gastric lesion group were higher than those in the non-gastric disease group (P < 0.05). In the gastric cancer group, patients with TNM stage Ⅲ to Ⅳ, moderately-lowly differentiated histological grade, and lymph node metastasis had higher serum levels of ProGRP and CA72-4 than those with stage Ⅰto Ⅱ, high differentiation, and no lymph node metastasis. Patients with moderately-lowly differentiated histological grade had higher serum levels of SCC than those with high differentiated histological grade (P < 0.05). After 24 months of follow-up, 49 patients survived (survival group) and 19 patients died (death group) in the gastric cancer group. The serum levels of ProGRP, SCC, and CA72-4 in the death group were higher than those in the survival group on admission (P < 0.05). Multivariate Logistic regression analysis showed that serum ProGRP, SCC, and CA72-4 were independent influencing factors for the prognosis of gastric cancer patients (P < 0.05). Serum ProGRP, SCC, and CA72-4 had good predictive efficacy for death during follow-up in gastric cancer patients (AUC=0.766, 0.705, 0.828), and their combined predictive efficacy was better (AUC=0.899). Conclusion The serum levels of ProGRP, SCC, and CA72-4 that are related to TNM stage, histological grade, and lymph node metastasis in patients with gastric cancer are abnormally elevated, and their combined detection has good predictive efficacy for death during follow-up.

Objective:To study a deep learning-based dual-modality fundus camera which was used to study retinal blood oxygen saturation and vascular morphology changes in eyes with branch retinal vein occlusion (BRVO).Methods:A prospective study. From May to October 2020, 31 patients (31 eyes) of BRVO (BRVO group) and 20 healthy volunteers (20 eyes) with matched gender and age (control group) were included in the study. Among 31 patients (31 eyes) in BRVO group, 20 patients (20 eyes) received one intravitreal injection of anti-vascular endothelial growth factor drugs before, and 11 patients (11 eyes) did not receive any treatment. They were divided into treatment group and untreated group accordingly. Retinal images were collected with a dual-modality fundus camera; arterial and vein segments were segmented in the macular region of interest (MROI) using deep learning; the optical density ratio was used to calculate retinal blood oxygen saturation (SO 2) on the affected and non-involved sides of the eyes in the control group and patients in the BRVO group, and calculated the diameter, curvature, fractal dimension and density of arteriovenous in MROI. Quantitative data were compared between groups using one-way analysis of variance. Results:There was a statistically significant difference in arterial SO 2 (SO 2 -A) in the MROI between the affected eyes, the fellow eyes in the BRVO group and the control group ( F=4.925, P<0.001), but there was no difference in the venous SO 2 (SO 2-V) ( F=0.607, P=0.178). Compared with the control group, the SO 2-A in the MROI of the affected side and the non-involved side of the untreated group was increased, and the difference was statistically significant ( F=4.925, P=0.012); there was no significant difference in SO 2-V ( F=0.607, P=0.550). There was no significant difference in SO 2-A and SO 2-V in the MROI between the affected side, the non-involved side in the treatment group and the control group ( F=0.159, 1.701; P=0.854, 0.197). There was no significant difference in SO 2-A and SO 2-V in MROI between the affected side of the treatment group, the untreated group and the control group ( F=2.553, 0.265; P=0.088, 0.546). The ophthalmic artery diameter, arterial curvature, arterial fractal dimension, vein fractal dimension, arterial density, and vein density were compared in the untreated group, the treatment group, and the control group, and the differences were statistically significant ( F=3.527, 3.322, 7.251, 26.128, 4.782, 5.612; P=0.047, 0.044, 0.002, <0.001, 0.013, 0.006); there was no significant difference in vein diameter and vein curvature ( F=2.132, 1.199; P=0.143, 0.321). Conclusion:Arterial SO 2 in BRVO patients is higher than that in healthy eyes, it decreases after anti-anti-vascular endothelial growth factor drugs treatment, SO 2-V is unchanged.

ObjectiveTo analyze the epidemiological characteristics of a family cluster of COVID-19 in a district of Shanghai， and to provide a scientific basis for prevention and control of cluster epidemic of COVID-19. MethodsField epidemiological survey was applied to study the cases and close contacts of a family cluster of COVID-19 in a district of Shanghai in 2021. Descriptive analysis of epidemiological survey data was conducted and real-time fluorescent quantification （RT-PCR） was used to detect new coronavirus nucleic acid for the collected specimens. ResultsCase A was the source of infection in the home aggregated epidemic. There were 2 second-generation cases infected in the whole incubation period. Case B and C were transmitted by case A through eating together. The PCR test results were negative both in the close contacts outside the family of primary contacts as well as in the close contacts to primary close contacts. ConclusionCOVID-19 is highly contagious and populations are generally susceptible. It is easy to cause family aggregated epidemic situation. Asymptomatic infection should be detected early and isolated. We should strengthen the tracking and management of close contacts of COVID-19 cases， and identify the second-generation cases as soon as possible.

Objective    To evaluate the prognosis of interventional treatment with covered stent graft for retrograde Stanford type A aortic dissection and intramural hematoma by single-arm meta-analysis. Methods    Related studies on treating retrograde Stanford type A aortic dissection and intramural hematoma with covered stent graft were retrieved from the databases by computer, including PubMed, EMbase, The Cochrane Library, Wanfang Data, VIP, CNKI and CBM, from inception to January 2020. Literatures were screened by researchers step by step according to the predefined inclusion and exclusion criteria. Quality of the enrolled literatures was evaluated, and data were extracted from the included studies. Afterwards, single-arm meta-analysis was carried out by the R3.6.3 software. Results    A total of 12 English and 5 Chinese studies were included, which were all case series, and the quality of all literatures was moderate evaluated by Newcastle-Ottawa Scale (NOS). After analyzing the clinical prognosis of 260 patients, the 30-day mortality was 6% (95%CI 0.04 to 0.11, P=0.97), the late mortality was 8% (95%CI 0.05 to 0.14, P=0.78), the incidence of endoleak was 21% (95%CI 0.16 to 0.29, P=0.06), the incidence of stroke was 5% (95%CI 0.03 to 0.09, P=0.99), the incidence of new aortic dissection was 7% (95%CI 0.04 to 0.11, P=0.96), the incidence of dissection progression was 10% (95%CI 0.07 to 0.16, P=0.24), and the absorption rate of intramural hematoma was 84% (95%CI 0.37 to 1.00, P<0.01). Conclusion    Interventional treatment with covered stent graft for retrograde Stanford type A aortic dissection and intramural hematoma can obtain good early treatment results for some patients, and can be used as a safe and effective treatment for aged patient with high risk who cannot tolerate surgery. Endoleak, stroke and new aortic dissection are the early serious complications of this method.

Objective To compare the efficacy and prognosis of epirubicin combined with paclitaxel and epirubicin combined with docetaxel in the treatment of breast cancer.Methods Patients in the study group were treated with epirubicin and paclitaxel, while the control group was treated with epirubicin plus docetaxel.Results The two groups of breast cancer patients by the end of the treatment were valid for 5 years of follow-up, five year survival rate(86.67%)than the control group(68.89%), the study group the recurrence rate(4.44%)than in the control group(15.56%), the data had significant differences(P<0.05).Conclusion The epirubicin is conducive to breast cancer patients for better disease control effect and prognosis than star, paclitaxel combined with chemotherapy.

Objective To investigate the effect of Avastin (bevacizumab) combined with preoperative FOLFOX neoadjuvant chemotherapy on the prognosis of patients with locally advanced rectal cancer (LARC).MethodsA total of 80 cases of patients with LARC treated with total mesorectal excision (TME) in our hospital from January 2013 to January 2016 were randomly divided into the control group and the observation group, 40 cases in each group.The control group were treated with preoperative FOLFOX chemotherapy while the observation group were treated with bevacizumab injection, based on the treatment in the control group.21 days was a cycle of chemotherapy, and both groups were treated for at least 4 cycles.After 6 cycles of chemotherapy, operation was carried out, following TEM principle.The short-term and long-term prognosis, rate of R0 resection, the incidence of postoperative complications and side effects of chemotherapy were compared between the two groups.ResultsThere was no significant difference between the two groups in the good response rate of chemotherapy, the rate of R0 resection, the incidence of postoperative complications, the 1-year and 3-year survival rates and 1-year disease-free survival rate.The incidence rates of gastrointestinal reactions and bone marrow suppression in the observation group were 52.5% and 52.5%, respectively while in the control group were 25.0% and 20.0%, respectively (P<0.05), but there was no significant difference in the incidence rates of grade Ⅲ~Ⅳ gastrointestinal reaction and bone marrow suppression between the observation group and the control group (5.0% and 15.0% vs 2.5% and 5.0%).The 3-year disease-free survival rate of the observation group was higher than that of the control group (82.5% vs 60.0%) (P<0.05).ConclusionThe application of bevacizumab combined with preoperative FOLFOX chemotherapy in the treatment of LARC can improve the 3-year disease-free survival rate, without increasing postoperative adverse reactions and serious side effects of chemotherapy.

BACKGROUND:On CT reconstruction of three-dimensional (3D) model, fracture virtual reduction and internal fixation cannot be achieved, and reasonable operation scheme cannot be formulated. Digital design can fuly meet the needs of clinical orthopedics physicians. Standard parts database can provide the possibility to choose the ideal internal fixation. 3D printing makes the reasonable operation scheme accurate in clinical implementation. OBJECTIVE:To discuss the feasibility, accuracy and minimal invasion of internal fixation in treatment of the distal femoral fracture with digital design of standard parts database by 3D printing. METHODS: (1) Nine adult lower extremity specimens were selected to take continuously thin-layer CT scanning. After Dicom images were imported into the mimics software, the model was established. According to the AO classification, they were classified into A1-3, B1-3 and C1-3 types of distal femoral fracture by virtual design. Internal fixation with plate and screw formed standard parts database virtualy. It was printed out the pilot hole of the navigation module design by three-dimensional printing forming technique. Plate and screw were inserted assisted by the module. X-ray and CT scan were taken postoperatively to access the position. (2) 30 patients with distal femoral fracture were subjected to above fixation. The operation time, intraoperative blood loss and postoperative drainage were recorded. Imaging and curative effects were evaluated during folow-up. RESULTS AND CONCLUSION: (1) Nine samples underwent X-ray and CT scan. 3D reconstruction results revealed plate position, screw entry point, nail direction, length and diameter were consistent with presetting data in Mimics software. The navigation models were designed to fit the lateral bony structure of distal femur. There were good fitting degree, good card position and good stability when the navigation was applied. It could guide plant and screw implantation. (2) In 30 cases, the operation time was (104.63±26.12) minutes, intraoperative blood loss was (121.74±11.49) mL, and postoperative drainage volume was (30.29±6.38) mL. Al patients were folowed up. According to Schagzker criterion, the efficiency of 22 cases was excelent, 6 cases good and 2 cases average, and the excelent and good rate was 93%. The parameters of length, diameter, orientation and angle were consistent with that preoperatively. (3) Internal fixation formed by standard parts database assisted by 3D printing navigation model has advantages of high accuracy, short process, lessened blood loss, high safety, less complications, and precise fixation. Digital design of standard parts database via3D printing navigation module is expected to achieve implant navigation and application.