Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options. This investigation examined the anti-cancer potential of Caerulomycin A (Cae A), a natural compound derived from marine actinomycetes, against TNBC. Cae A demonstrated selective inhibition of viability and proliferation in TNBC cell lines, including 4T1, MDA-MB-231, and MDA-MB-468, through apoptosis induction. Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum (ER) stress and subsequent upregulation of C/EBP homologous protein (CHOP) expression, resulting in mitochondrial damage-mediated apoptosis. Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis, highlighting the essential role of ER stress and CHOP in Cae A's anti-tumor mechanism. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) decreased in TNBC cells following Cae A treatment, indicating reduced mitochondrial respiratory and glycolytic capacities. This diminished energy metabolism potentially triggers ER stress and subsequent apoptosis. Furthermore, Cae A exhibited significant anti-tumor effects in the 4T1 tumor model in vivo without apparent toxicity. The compound also effectively inhibited human TNBC organoid growth. These results indicate that Cae A may serve as a potential therapeutic agent for TNBC, with its efficacy likely mediated through the disruption of glucose metabolism and the induction of ER stress-associated apoptosis.
Humans ; Endoplasmic Reticulum Stress/drug effects* ; Triple Negative Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Female ; Animals ; Glucose/metabolism* ; Mice ; Cell Proliferation/drug effects* ; Transcription Factor CHOP/genetics* ; Antineoplastic Agents/pharmacology* ; Mitochondria/metabolism* ; Mice, Inbred BALB C

Objective:To translate the Cumulated Ambulation Score (CAS) into Chinese and test its reliability and validity in elderly inpatients, to provide a basis for assessing elderly inpatients′ basic mobility during hospitalization.Methods:This was a cross-sectional study. After obtaining the authorization of the original author, the Chinese version of CAS was formed by WHO′s cross-cultural translation process. A total of 414 hospitalized elderly inpatients from Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, and Shanghai Yangpu District Kongjiang Hospital were selected between March and September 2021. Cronbach′s α coefficient was used to test internal consistency, linear weighted Kappa was employed to assess inter-rater reliability, and concurrent validity was examined using items related to mobility of Barthel Index scores as a reference standard.Results:Of the 414 patients, 221 were males and 193 were females, and the patients aged (76.67 ± 9.98) years old; 122 cases (29.5%) had a perfect score of 6 with normal basic mobility, 89 cases (21.5%) had a score of 0 with complete loss of mobility, and the remaining 203 patients had a score of 1-5 with varying degrees of reduced mobility. The Chinese version of CAS demonstrated good assessment performance for basic mobility in elderly inpatients with a Cronbach′s α coefficient of 0.952. Weighted Kappa values for individual items and total scores showed excellent agreement among raters (>0.85), while concurrent validity yielded a value of 0.935 ( P<0.01) when compared with Barthel Index scores.Total score of CAS was significantly correlated with item scores and total score of Barthel index ( r values were 0.423 to 0.944, all P<0.01). Conclusions:The Chinese version of CAS has good reliability and validity. The items are concise, clear and easy to understand. It is suitable as a preliminary screening tool for clinical departments to evaluate the basic mobility of elderly inpatients.

Objective: 18F-N-(2-(Diethylamino)ethyl)-5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy) picolinamide ( 18F-PFPN) is a novel positron emission tomography (PET) probe designed to specifically targets melanin. This study aimed to evaluate the diagnostic feasibility of 18F-PFPN in patients with ocular or orbital melanoma. Materials and Methods: Three patients with pathologically confirmed ocular or orbital melanoma (one male, two females; age 41–59 years) were retrospectively reviewed. Each patient underwent comprehensive 18F-PFPN and 18F-fluorodeoxyglucose ( 18F-FDG) PET scans. The maximum standardized uptake value (SUV max) of the lesion and the interference caused by background tissue were compared between 18F-PFPN and 18F-FDG PET imaging. In addition, the effect of intrinsic pigments in the uvea and retina on the interpretation of the results was examined. The contralateral non-tumorous eye of each patient served as a control. Results: All primary tumors (3/3) were detected using 18F-PFPN PET, while only two primary tumors were detected using 18F-FDG PET. Within each lesion, the SUV max of 18F-PFPN was 2.6 to 8.3 times higher than that of 18F-FDG. Regarding the quality of PET imaging, the physiological uptake of 18F-FDG PET in the brain and periocular tissues limited the imaging of tumors. However, 18F-PFPN PET minimized this interference. Notably, intrinsic pigments in the uvea and retina did not cause abnormal concentrations of 18F-PFPN, as no anomalous uptake of 18F-PFPN was detected in the healthy contralateral eyes. Conclusion Compared to 18F-FDG, 18F-PFPN demonstrated higher detection rates for ocular and orbital melanomas with minimal interference from surrounding tissues. This suggests that 18F-PFPN could be a promising clinical diagnostic tool for distinguishing malignant melanoma from benign pigmentation in ocular and orbital melanomas.

Objective:To investigate the correlation between variations in mitochondrial DNA (mtDNA) control region (D-loop) and keloids.Methods:A total of 216 patients with keloids were collected from Department of Dermatology, the First Affiliated Hospital of Kunming Medical University from 2016 to 2019. Total DNA was extracted from peripheral blood samples of all the patients, as well as keloid tissues and perilesional normal skin tissues of 25 patients with keloids. Peripheral blood samples were collected from 299 health checkup examinees without keloids in Health Examination Center, the Affiliated Hospital of Yunnan University, who served as controls. PCR amplification and Sanger sequencing were performed on the mtDNA D-loop region, and mutation sites in each sample were analyzed by comparisons with the revised Cambridge Reference Sequence (rCRS) . Haplogroups were assigned in the 2 groups by using Phylotree-mtDNA tree Build 17. Mutations in the mtDNA D-loop region were compared among keloid tissues, perilesional normal skin tissues and peripheral blood samples. A median-joining network was constructed via network 5.0 software. Binary logistic regression analysis was performed to investigate the correlation between haplogroup frequencies and the occurrence of keloids, and chi-square, t and t′ tests were used to analyze clinical data. Results:Among the 216 patients with keloids, variations in mtDNA D-loop region were classified into 10 haplogroups, including A, B, D, R9, G, M*, M7, M8, M9 and N9, with the haplogroups R9 and M9 showing the highest (21.3%, 46/216) and lowest (0.9%, 2/216) frequencies respectively. The frequencies of haplogroups M7 ( P=0.040, OR=0.248, 95% CI: 0.066 - 0.937) and N9 ( P=0.048, OR=0.191, 95% CI: 0.037-0.986) were significantly lower in the patients with keloids than in the controls. The median-joining network plot showed that the distribution pattern of the haplogroup M7 differed between the patients with keloids and controls. Significantly less number of lesional sites and younger age of onset were observed in the patients with haplogroup M7 compared with those with non-M7 haplogroups ( P=0.000 1, 0.045, respectively) . Conclusion:The haplogroup M7 is correlated with the occurrence of keloids, and may be a potential protective factor for keloid formation.

Objective This study was aimed to investigate the effects of ω-3 polyunstaurated fatty acids (ω-3 PUFAs) on the growth of gastric cancer cells in nude mice,and to find whether the Ros homolog gene Rho-associated coiled-coil containing protein kinase 1 (RHO-ROCK1) signaling pathway is involved.Methods 16 BALB/C nude mice were injected subcutaneously with SGC7901 gastric cancer cells to establish the tumor-bearing mouse model.The mice were randomized:control group (normal saline) and intervention group (ω-3 PUFAs).The mRNA expression of Ros homolog gene family,member A (RHOA),RHOC,and ROCK1 in tumor tissue were detected by quantitative polymerase chain reaction (qPCR).Immunofluorescence and Western blot were used to detect RHOA,RHOC,and ROCK1 protein expression.Results The volume and weight of the tumors in the ω-3 PUFAs group were slightly smaller than that in the control group (P ＞ 0.05).Compared to the control group,hematoxylin and eosin staining showed multifocal tumor necrosis in the ω-3 PUFAs group,while the tumors of the control group showed abundant blood supply.qPCR and Western blot showed that the mRNA and proteins expression of RHOA and ROCK1 in the ω-3 PUFAs group was significantly lower than those in the control group (P ＜ 0.05).The immunofluorescence redults also showed that the expression of these proteins in the ω-3 PUFAs group was slightly lower than that in the control group.Conclusions These results suggested that ω-3 PUFAs may affect the growth of gastric cancer in nude mice by affecting the expression of RHOA,RHOC and ROCK1,thus inhibiting the excessive proliferation of gastric cancer cells and leading to tumor necrosis.

Objective:To evaluate the association between brachial-ankle pulse wave velocity ( ba-PWV) and metabolic syndrome ( MetS) among the Chinese elderly and the gender difference .Methods:We conducted a population-based cross-sectional study in a representative urban area of Beijing , China. A sample of 2 102 community elderly (848 males, and 1 254 females) aged 60 to 95 years were included in the study .MetS was defined according to the 2009 harmonizing definition .Results:The prevalence of MetS was 59.1% (50.1% in males and 65.2% in females, P<0.001).The baPWV value was be-tween 8.2 to 45.6 (20.0 ±4.4) m/s, and showed an increasing trend with age (P<0.001).The par-tial correlation showed baPWV was positively associated with BMI (r =0.076, P =0.037), systolic blood pressure (r=0.380, P<0.001), diastolic blood pressure (r=0.276, P<0.001), triglyceride (r=0.040, P=0.046), fasting blood glucose (r=0.140, P<0.001), 2-hour post-meal blood glu-cose (r=0.121, P<0.001), and negatively associated with HDL-C (r=-0.128, P=0.048).There was a strong association between baPWV and prevalence of MetS and its component number in females but not in males .Compared with the lowest quartile of baPWV , the adjusted ORs were 1 .22 ( 95%CI 0.83-1.79), 1.32(95%CI 0.90-1.93), 1.46(95%CI 1.00-2.14) in males and 1.28(95%CI 0.93-1.77), 1.55(95%CI 1.12 -2.16), 1.86(95%CI 1.32-2.61) in females for the second, third and top quartiles .Conclusion:The prevalence of MetS increases substantially with increasing levels of baPWV among the Chinese elderly , especially in females .

Objective To study the set-up errors by CBCT in IMRT with two different immobilization techniques for thoracic and abdominal tumors.Methods Sixty patients with thoracic and abdominal tumor were included in this study and separated into study group and the control group.The study group were immobilized with carbon fiber holder,vacuum bag and thermoplastic mask.The control group were immobilized with carbon fiber holder and thermoplastic mask.CBCT scan and auto-match online were regularly performed before the treatment.The setup of left-right(x),superior-inferior(y),anterior-posterior (z) were received.The value of the Mptv was calculated,meanwhile.The grouped t-test of was carried out between these two methods.Results The shift errors in x-,y-,z-dimension of the study group were (0.32 ± 2.58) mm,(-0.40 ± 3.89) mm,(-0.75 ± 2.43) mm.The Mrrv were 5.60 mm,6.08 mm,6.32 mm.The translation set-up errors in x-,y-,z-dimension of the control group were(0.62 ±3.60),(2.44 ± 4.93),(0.66 ±2.85) mm,respectively.The MPrv were 8.07,10.63,6.90 mm,respectively.The t-test value were t =-0.78,-5.11,-4.22,P =0.440,0.000,0.000,respectively.Conclusions The immobilization techniques with carbon fiber holder,vacuum bag and thermoplastic mask would be better than the techniques without the vacuum bag in reducing the setup errors.

Cone-beam CT (CBCT) of Elekta can be used to analyze the setup errors in intensity modulated radiotherapy. A total of 240 patients with head and neck cancer were chosen in the period from October, 2009 to October, 2010. Their CBCT images were obtained after initial setup, and registered to the planning CT images, and then the setup errors on translational directions (X, Y, Z) and on rotational directions (U, V, W) were obtained and analyzed. The results showed that the setup errors on translational directions in Y-axis and Z-axis were larger than in X-axis, and the setup errors on rotational directions in Y-axis was much more obvious than those on the other two directions, which should be taken care during the patient daily setup. It may be concluded that the CBCT system can improve the precision for radiotherapy.
Cone-Beam Computed Tomography ; methods ; Head and Neck Neoplasms ; diagnostic imaging ; radiotherapy ; Humans ; Radiotherapy Setup Errors ; prevention & control ; statistics & numerical data ; Radiotherapy, Intensity-Modulated

Objective To investigate the reversal effect and the mechanism of sodium norcantharidate(SNCTD)on human lung adenocarcinoma cell line A549/DDP. Methods CKK assay was used to screen out non-toxic concentration (less than 10 percent of cell inhibition ratio) of SNCTD, and to measure the IC50 of cisplatin and IC50 of innoxious concentration SNCTD plus cisplatin in drug-resistant cell line. The accumulation effect of Rh123 was assayed by flow cytometry after treatment with non-toxic concentration of SNCTD. PT-PCR was used to detect the expression of mdr1, MRP1 gene for the drug-resistant cell line treated with non-toxic concentration of SNCTD for 48h. Results (1)The non-toxic concentration of SNCTD was 5μg/ml. SNCTD could decrease drug resistance to cisplatin. The reversal fold was 1.97. (2)The fluorescence intensity of Rh123 in the cells treated with 5μg/ml SNCTD was obviously increased (F=36.99, P＜0.05). (3)The expressions of mdr1, MRP1 gene decreased significantly in a concentration-dependent manner.Conclusions SNCTD could reverse the resistance to cisplatin in A549/DDP cell line. It possibly downregulates the expression of mdr1, MRP1 gene, and inhibits the function of efflux pump of membrance protein.