Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

Purpose To study the clinical and pathological features of angiomatoid fibrous histocytoma(AFH)and to ex-plore its diagnosis,differential diagnosis and prognosis.Meth-ods The clinicopathological and follow-up data were analyzed in 14 cases of AFH,and the literatures were reviewed.Results There were 11 males and 3 females.The age ranged from 11 months to 12 years and 11 months,with average 5.9 years.3 cases were located in limbs,and 5 cases in trunk,5 cases in head and neck region,and 1 of intracranial tumor.Histological-ly,14 cases were composed of fibrous capsules and lymphocyte sheaths,and cell nucleus were vacuolar,forming fascicles with focal whirling and synteny.Intralesional pseudoangiomatous spaces were noted in 9 cases.Calcification was found in 2 ca-ses.2 cases showed high mitotic acticity(11/10 HPF).Scle-rosing and/or myxoid stroma was seen in 3 cases.Tumors were immunopositive for desmin(10/14),EMA(12/14),CD99(12/14),SMA(9/12),ALK(7/8),and the average of Ki67 index was 16％.7 cases harbored EWSR1 rearrangenent(part-ner gene not identified),2 cases had EWSR1-ATF1 fusion and 2 EWSR1-CREB1 fusion.Clinical follow-up information was a-vailable for 14 cases(average 46 months).All the 14 cases were alive without recurrence and metastasis.Conclusion AFH is a borderline or low-grade malignant tumor,often demon-strates indolent behavior in children,but rarely recurs and me-tastasizes.The diagnosis and differential diagnosis require a comprehensive analysis of clinical features,histopathologic changes,immunohistochemical finding and EWSR1 or FUS gene detection results.

Objectives:To explore the safety and accuracy of subaxial cervical pedicle screw(CPS)insertion assisted with optimized 3D-printed drill guiding template(DGT).Methods:A retrospective study was conducted to analyze the clinical data of 42 patients aged 32-74 years(50.1±9.8 years)who underwent posterior cervi-cal pedicle screw intemal fixation between August 2016 and October 2022.The patients were followed up for 13-25 months(19.6±3.2 months).They were divided into two groups of guiding template group(n=22)and free-hand group(n=20)according to the method of pedicle screw insertion.In the guiding template group,the sub-axial CPSs insertions were assisted with 3D-printed DGT,designed individually for each patient based on the design scheme of an optimized pedicle drill guiding template,and the patients consisted of 12 males and 10 females,among which 6 patients were with cervical spine injury or spinal cord injury,9 were with ossifica-tion of posterior longitudinal ligament(OPLL),5 were with intraspinal tumor,and 2 were with cervical spondy-lotic myelopathy.In the free-hand group,the subaxial CPSs were inserted with free hand according to the cervical parameters such as pedicle angle and diameter on the CT images measured before operation,and the patients consisted of 10 males and 10 females,among which 4 patients were with cervical spine injury or spinal cord injury,10 with OPLL,5 with intraspinal tumor,and 1 with cervical spondylotic myelopathy.There were no significant differences in sex,age,disease,and preoperative visual analogue scale(VAS)score and Japanese Orthopaedic Association(JO A)score between the two groups(P＞0.05).The operative time,intraopera-tive blood loss,and postoperative 12 months of VAS and JOA scores were recorded and compared.CT scan was performed at 1 week after operation on cervical spine,and the accuracy of pedicle screw placement was evaluated in accordance with Kaneyama's evaluation method:Grade 0,screw was contained in the pedicle;Grade 1,screw penetrated pedicle＜50％of the screw diameter;Grade 2,screw penetrated pedicle＞50％of the screw diameter;Grade 3,screw completely penetrated the pedicle.Grades 0 and 1 were considered accurate placement,and grades 2 and 3 were considered misplacement.The perioperative complications were recorded for each patient in the two groups.Results:The operative time,intra-operative blood loss in guiding template group(102.2±16.1min,89.3±17.7mL)were statistically less than those in free-hand group(142.8±20.9min,133.3±34.0mL)(P＜0.01).A total of 216 CPSs were placed:118 in the guiding template group,including 90 screws of grade 0,22 screws of grade 1,5 screws of grade 2,1 screw of grade 3,with an accuracy rate of 94.9％(112/118);And 98 in the free-hand group,including 48 screws of grade 0,36 screws of grade 1,10 screws of grade 2,and 4 screws of grade 3,with an accuracy rate of 85.7％(84/98).The accuracy rate of pedicle screw insertion was significant higher in the guiding template group than that in the free-hand group(P＜0.05).No major neurovascular complications nor internal fixation loosening or breakages were observed in two groups of patients.At 12 months after operation,the VAS score in both groups was statistically less than that before operation(P＜0.01),and the JOA score in both groups was statistically more than that before opera-tion(P＜0.01),and there were no significant differences in VAS score and JOA score between groups,respec-tively(P＞0.05).Conclusions:The optimized design scheme of 3D-printed DGT is helpful in improving the ac-curacy and safety of subaxial CPS insertion.

Objective To investigate the clinical efficacy of endovascular intervention in the treatment of acute ischemic stroke caused by carotid stump syndrome(CSS).Methods A retrospective analysis was performed for the patients with anterior circulation acute ischemic stroke who underwent endovascular intervention in The First Hospital of Jilin University from August 2018 to October 2022,among whom the patients with acute ischemic stroke caused by CSS were identified,and related data were collected for these patients,including demographic information,risk factors,surgery-related characteristics,and prognosis.Results A total of 23 patients met the diagnostic criteria for CSS,among whom 19 patients achieved successful revascularization and 7 achieved extended Thrombolysis in Cerebral Infarction(eTICI)grade 3.Fourteen patients received concurrent carotid artery stenting.Twelve patients experienced intracranial hemorrhage after surgery,among whom 1 patient experienced symptomatic intracranial hemorrhage(sICH)leading to in-hospital death.On day 90 after onset,8 patients achieved functional independence,with a modified Rankin Scale score of≤2,while 4 patients died within 90 days.Conclusion CSS is a clinical syndrome caused by embolization from the occluded distal portion of the internal carotid artery.Endovascular intervention is an effective method for the treatment of CSS.

Objective:To investigate the implementation procedures and dosimetric verification of the first patient treated with total body irradiation (TBI) based on volumetric modulated arc therapy (VMAT).Methods:Two sets of CT images were acquired under the head-in first and foot-in first to contour the planning target volume (PTV) of the cranial and caudal segments to accomplish the treatment of the whole body length, on which two interrelated plans of 5 subsequent isocenters with a total of 15 VMAT fields were performed to cover all PTVs. The plans were prescribed to ensure 90% PTV dose coverage with a total dose of 12 Gy in 6 fractions. Firstly, a dose optimization was performed on the caudal CT images, then the cranial CT images were optimized based on the dose distribution of the caudal CT images. The evaluation of the final treatment plan was carried out based on a plan sum of both two sets of images. The parameters of PTV and organs at risk (OARs) were measured by dose volume histograms from the accumulated plan. The quality assurance comprised the verification of the VMAT plans for each individual isocenter via Delta4 phantom. The dose distribution in the overlapped region between two adjacent central fields was verified with EBT3 film. The absolute dose at the overlapped region between two images was measured via Pinpoint chamber. In vivo dosimetry on the patient′s skin was monitored by MOSFET dosimeters. The results of planning parameters and treatment duration were analyzed. Results:The mean doses of two segments of PTVs were 12.45 Gy and 12.37 Gy. The mean dose for the lung was 10.8 Gy. The machine unit (MU) and mean treatment delivery time were 2 883 MU and 24.3 min, and the mean total time per fraction was 121 min. The mean 3%/3 mmγ-analysis pass rate for each isocenter VMAT plan was (99.74±0.42)%, and the mean 5%/5 mmγ-analysis pass rate for the overlapped region was (90.11±2.72)%. The average deviation of absolute dose in the overlap region of the caudal and cranial images was (3.6±0.4)%. In vivo measurement of 8 points on the patient showed that the dose of each region was ranged from 1.57 Gy to 2.04 Gy. Conclusion:According to the results of dosimetric verification, TBI based on multi-isocenter VMAT can be applied in clinical practice, which remains to be improved in terms of dose distribution, measurement results and clinical efficiency.

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and represent the major cause of postsurgical morbidity. Enterolysis at repeat surgeries induces adhesion reformation that is more difficult to prevent than primary adhesion. Here we studied the preventive effects of different approaches of berberine treatment for primary adhesion, and its effects on adhesion reformation compared to Interceed. We found the primary adhesion was remarkably prevented by berberine through intraperitoneal injection 30 min before abrasive surgery (pre-berberine) or direct addition into injured cecum immediately after the surgery (inter-berberine). Rats with adhesion reformation had a more deteriorative collagen accumulation and tissue injury in abrasive sites than rats with primary adhesion. The dysregulated TIMP-1/MMP balance was observed in patients after surgery, as well as adhesion tissues from primary adhesion or adhesion reformation rats. Inter-berberine treatment had a better effect for adhesion reformation prevention than Interceed. Berberine promoted the activation of MMP-3 and MMP-8 by directly blocking TIMP-1 activation core, which was reversed by TIMP-1 overexpression in fibroblasts. In conclusion, this study suggests berberine as a reasonable approach for preventing primary adhesion formation and adhesion reformation.

Objective To study epidemic of schistosomiasis in the Qiandao Lake reservoir area,and to provide a reference for prevention and control of schistosomiasis in the construction of large water conservancy projects in the epidemic area of schistosomiasis.Methods The data over the years of snail condition and monitoring of schistosomiasis before and after building the dam,and water conservancy project reconstruction related information were collected.Based on the survey results of the river channel,the lake beach and the dissipation zone in the reservoir area,the influence of Xin'an River water conservancy project on epidemic of schistosomiasis in the Qiandao Lake reservoir area was analyzed,and the epidemic factors of the schistosomiasis in the Three Gorges reservoir were compared and analyzed.Results Before the dam was built,an area of 38 144 000 m2 was examined but Oncomelania was undetected.The Qiandao Lake reservoir area belonged to a non epidemic area of schistosomiasis.After the dam was built,557 cases of schistosomiasis were found in 6 232 immigrants during 1962-1965,resulting in an imported epidemic.In 1970-1980,an area of 379 654 m2 in which Oncomelania was found was examined and snails were mainly distributed in some rice fields and ditches in the end of the reservoir.949 cases of local schistosomiasis were found in the snails.The condition and condition of the snail are gradually controlled through several decades of comprehensive prevention and control.Compared with the epidemic factors of schistosomiasis in Qiandao Lake and the Three Gorges reservoir,the environment of elevation beach and ecologically fragile fluctuation zone coexist in the two reservoir areas.Conclusion From the long-term longitudinal monitoring data of the Qiandao Lake reservoir area and the epidemic regularity of schistosomiasis and the comparison with the ecology of the Three Gorges reservoir,it is concluded that the two reservoir areas will not cause a large range of schistosomiasis epidemic in general,but it does not exclude the possibility of the breeding of the inputting Oncomelania.

Objective To investigate the effect of carotid sympathetic nerve net stripping operation in treating children patients with spastic unilateral cerebral palsy and its effect on motor function.Methods Seventy-six children cases of spastic unilateral cerebral palsy were divided into the control group and observation group.On the basis of routine therapy,the former was treated with type A botulinum toxin,while the latter used the carotid sympathetic nerve netting operation for the treatment.After 6-month treatment,the improvement degree of the Comprehensive Functional Rating Scale of Cerebral Palsy Children,Gross Motor Function Measure(GMFM) score and Ashworth spasm grade were compared between the two groups.Results after 6-month treatment,the improvement degrees of the Comprehensive Functional Rating Scale of Cerebral Palsy Children,GMFM scores and Ashworth spasm grade in the observation group were significantly greater than those in the control group,the difference was statistically significant (P＜0.05).Conclusion The carotid sympathetic nerve net stripping operation in treating children patients with spastic unilateral cerebral palsy has significant effect and is worthy to be popularized in clinic.