Triple-negative breast cancer is therapeutically challenging due to the low expression of tumor markers and 'cold' tumor immunosuppressive microenvironment. Here, we present a dual-targeting peptide-drug conjugate (PDC) for tumor inhibition. Our PDC efficiently and selectively delivers cytotoxic Monomethyl Auristatin E (MMAE) into tumor cells via C-X-C chemokine receptor type 4 (CXCR4) and folate receptor 1 (FOLR1) for synergistic inhibition of growth and metastasis. Our results show that the dual-targeting PDC has potent antitumor activity in cultured human cells and several murine transplanted tumor models without apparent toxicity. The combination of dual-targeting PDC and radiotherapy modulates the tumor immunosuppressive microenvironment by increasing CD8⁺ T cell infiltration and attenuating the proportion of myeloid-derived suppressor and regulatory T cells. Therefore, our dual-targeting PDC represents a promising new strategy for cancer therapy that rebalances the immune system and promotes tumor regression.

Objective:To investigate relationships between serum growth differentiation factor 15 (GDF15) and glycolipid metabolism in patients with metabolic associated fatty liver disease (MAFLD).Methods:The current investigation was a cross-sectional study. A total of 333 patients from the Fengxian District Central Hospital were recruited into the study after physical examination from February 2020 to February 2021. There were 107 patients with MAFLD and type 2 diabetes mellitus (T2DM), including 54 males and 53 females with a mean age of (57±11) years. There were 65 patients with simple MAFLD only, including 32 men and 33 women with a mean age of (49±5) years. There were 105 patients with T2DM only, including 53 men and 52 women, with a mean age of (56±10) years. A control group of 56 people without MAFLD or diabetes,28 male, 28 female, mean age (48±6) years, was also included in the study. Serum GDF15 was measured via enzyme-linked immunosorbent assays. IBM SPSS 26.0 was used for statistical analysis. Logistic regression was used to evaluate relationships between GDF15 and metabolic abnormalities in MAFLD patients.Results:GDF15 progressively increased in the control [385 (296, 484) ng/L], nonobese MAFLD [388 (319, 435) ng/L], obese MAFLD [426 (354, 527) ng/L], T2DM [664 (483, 900) ng/L], and MAFLD+T2DM groups [770 (560, 1 074) ng/L]( H=113.82, P=0.001). There was no significant difference in serum GDF15 between the simple MAFLD [406 (339, 524) ng/L] and control group ( U=1 505.50, P=0.132). GDF15 was significantly higher in the MAFLD+T2DM group than in the T2DM-only group ( U=4 573.50, P=0.019). In logistic regression analysis increased GDF15 was associated with increased risks of simple MAFLD [odds ratio ( OR)=2.202], T2DM ( OR=29.656), and MAFLD+T2DM( OR=58.197). In patients with MAFLD, serum GDF15 was higher in the FIB4 index>1.45 group [773 (534, 1 162) ng/L] than in the FIB4 index<1.45 group [527 (389, 787) ng/L] ( U=1 709.50, P<0.001). Increased GDF15 was associated with an increased risk of advanced liver fibrosis ( OR=2.388). Conclusion:In patients with simple MAFLD, GDF15 level was not significantly higher than in the control group. In the T2DM-only group and the MAFLD+T2DM group GDF15 was significantly higher than in the control group. Increased serum GDF15 was associated with increased risk and severity of MAFLD complicated with abnormal glucose and lipid metabolism. High GDF15 increased the risk of advanced fibrosis in MAFLD patients.

BACKGROUND: The relationship between quality of life at three months after lung cancer surgery and different surgical approaches is remains unclear. This study aimed to compare the quality of life of patients three months after uniportal and multiportal thoracoscopic lobectomy. METHODS: Data from patients who underwent lung surgery at the Department of Thoracic Surgery, Sichuan Cancer Hospital between April 2021 and October 2021 were collected. The European Organization for Research and Treatment of Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29) were used to collect quality of life data of the patients. Potential confounding factors in the baseline data were included in a multivariate regression model for adjustment, and the quality of life of the two groups three months postoperatively was compared with traditional clinical outcomes. RESULTS: A total of 130 lung cancer patients were included, with 57 males (43.8%) and 73 females (56.2%), and an average age of (57.1±9.5) yr. In the baseline data of the two groups, there was a statistical difference in the number of chest drainage tubes placed (P<0.001). After adjustment with the regression model, at three months postoperatively, there were no significant differences in all symptoms and functional status scores between the two groups (all P>0.05). The multiportal group had longer surgery time (120.0 min vs 85.0 min, P=0.001), postoperative hospital stay (6.0 d vs 4.0 d, P=0.020), and a higher incidence of early ≥ grade 2 complications (39.0% vs 10.1%, P=0.011) compared to the uniportal group. CONCLUSIONS Patients undergoing uniportal and multiportal thoracoscopic lobectomy have similar quality of life at three months postoperatively. The uniportal group may have certain advantages in terms of traditional clinical outcome indicators such as operation time, postoperative hospital stay, and early postoperative complications.
Male ; Female ; Humans ; Lung Neoplasms/surgery* ; Quality of Life ; Thoracic Surgery, Video-Assisted/adverse effects* ; Pneumonectomy/adverse effects* ; Postoperative Complications/surgery* ; Retrospective Studies

Objective:To investigate the anatomic mechanism and risk factors of intracranial embolism caused by injection at temporal region.Methods:(1) Latex perfusion was performed on the vessels of 8 cranial specimens. The vessels from the superficial temporal artery to the carotid artery were dissected to measure the length, the diameter of starting point and ending point and the volume of vessels (drainage method). (2) Cranial CT angiography of 20 patients (excluding patients with cervical diseases) were obtained from the database of Zhejiang Provincial People’s Hospital from January 2021 to December 2022. The length, the diameter of starting point and ending point, and the volume of vessels were measured. (3) 5 plastic surgeons used pressure simulation measuring equipment to vigorously press the temporal region of the real skull model according to the clinical practice and maintain 2 s to obtain the maximum pressure value. The additional pressure on the temporal region was obtained by subtracting the common carotid artery base pressure [set at 90, 120, 150 and 200 mmHg (1 mmHg = 0.133 kPa)] from the maximum pressure.Results:(1) 8 arteries were collected from 4 skull specimens. The length of vessels was (169.5±7.2) mm, the diameter of the starting point of vessel was (4.29±0.28) mm, the diameter of the ending point of vessel was (1.31±0.15) mm, and the volume was (1.56±0.21) ml. (2) There were 11 males and 9 females among 20 patients aged 23-53 years. The length of vessels was (172.2±7.6) mm, the diameter of the starting point of vessel was (5.63±0.43) mm, the diameter of the ending point of vessel was (1.77±0.16) mm, and the volume was (1.59±0.23) ml. (3) The mean value of additional pressure generated by local pressure on the temporal region by 5 physicians was (127.2±10.1) mmHg (113.8-138.6 mmHg).Conclusion:When the injection volume into the superficial temporal artery was more than 1.6 ml, the artery was damaged, and the temporal area was pressed strongly (the local pressure was more than 110 mmHg above the basic pressure), the injection material might flow into the intracranial from the junction of the common carotid artery and into the internal carotid artery, which was the possible mechanism of the temporal filling leading to intracranial embolism.

Objective:To investigate the anatomic mechanism and risk factors of intracranial embolism caused by injection at temporal region.Methods:(1) Latex perfusion was performed on the vessels of 8 cranial specimens. The vessels from the superficial temporal artery to the carotid artery were dissected to measure the length, the diameter of starting point and ending point and the volume of vessels (drainage method). (2) Cranial CT angiography of 20 patients (excluding patients with cervical diseases) were obtained from the database of Zhejiang Provincial People’s Hospital from January 2021 to December 2022. The length, the diameter of starting point and ending point, and the volume of vessels were measured. (3) 5 plastic surgeons used pressure simulation measuring equipment to vigorously press the temporal region of the real skull model according to the clinical practice and maintain 2 s to obtain the maximum pressure value. The additional pressure on the temporal region was obtained by subtracting the common carotid artery base pressure [set at 90, 120, 150 and 200 mmHg (1 mmHg = 0.133 kPa)] from the maximum pressure.Results:(1) 8 arteries were collected from 4 skull specimens. The length of vessels was (169.5±7.2) mm, the diameter of the starting point of vessel was (4.29±0.28) mm, the diameter of the ending point of vessel was (1.31±0.15) mm, and the volume was (1.56±0.21) ml. (2) There were 11 males and 9 females among 20 patients aged 23-53 years. The length of vessels was (172.2±7.6) mm, the diameter of the starting point of vessel was (5.63±0.43) mm, the diameter of the ending point of vessel was (1.77±0.16) mm, and the volume was (1.59±0.23) ml. (3) The mean value of additional pressure generated by local pressure on the temporal region by 5 physicians was (127.2±10.1) mmHg (113.8-138.6 mmHg).Conclusion:When the injection volume into the superficial temporal artery was more than 1.6 ml, the artery was damaged, and the temporal area was pressed strongly (the local pressure was more than 110 mmHg above the basic pressure), the injection material might flow into the intracranial from the junction of the common carotid artery and into the internal carotid artery, which was the possible mechanism of the temporal filling leading to intracranial embolism.

[This corrects the article DOI: 10.1016/j.apsb.2019.01.003.].

Objective:To search, evaluate and summarize the best evidences related to induction of labor by oxytocin infusion in pregnant women with full-term pregnancy, and to provide reference for clinical practice in order to reduce the complications during labor, such as the proportion of instrument delivery, prolonged labor duration, uterine rupture, postpartum hemorrhage, etc. Standardize the management process of induction of labor with oxytocin, improve the satisfaction of pregnant women to participate in the decision of induction of labor, and improve the outcome of the newborn.Methods:Take the evidence-based nursing method, in view of the full-term pregnancy pregnant women oxytocin drip induced labor evidence-based labor management problems, nearly 10 years related literature retrieval from January 1st 2011 to April 9th, 2021, the Australian JBI evidence-based health care center of literature quality evaluation criteria and evidence classification system, all kinds of research evaluation and classification of retrieval.Results:Early detection to 340 articles, and eventually into 9 articles, including 1 clinical decision, 6 guides, 2 pieces of system evaluation. Totally 45 pieces evidences related to induction of labor by oxytocin infusion in pregnant women with full-term pregnancy were sumarized, including induced labor time, oxytocin side effects, induced labor before evaluation, induced labor of guardianship, infusion solution, such as health education, and other seven aspects.Conclusions:The present study summarized 45 pieces of best evidence on the management of labor induced by oxytocin infusion during term pregnancy, which provided some evidence-based basis for midwives, obstetric nurses and managers. Through the application of the best evidence, it is beneficial to improve the outcome of pregnant women in the neonatal perinatal period, standardize the process of inducing labor with oxytocin, and improve the quality of obstetric care.

Objective:Diagnostic value assessment of sternal bone marrow cell morphology in patients with acquired hypocellular bone marrow failure syndromes (BMFS) characterized by normal cytogenetics.Methods:A total of 194 eligible patients with an acquired hypocellular BMFS pre-sternum diagnosis in Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science & Peking Union Medical College from June 2014 to January 2019 were reviewed. Sternal bone marrow evaluation was performed, and a post-sternum diagnosis was made. Clinical characteristics and overall survival (OS) were then compared among patients with different post-sternum diagnosis. Binary logistic regression was used to develop a predictive scoring system.Results:In 152 patients with pre-sternum AA diagnosis, 29 patients with a pre-sternum idiopathic cytopenia of undetermined significance (ICUS) diagnosis, and 13 patients with a pre-sternum clonal cytopenia of undetermined significance (CCUS) diagnosis, sternal bone marrow evaluation resulted in a change of diagnosis to hypocellular myelodysplastic syndrome (hypo-MDS) in 42.8% (65/152) , 24.1% (7/29) , and 30.8% (4/13) , respectively. Patients with a post-sternum hypo-MDS diagnosis showed a significant difference in OS compared with patients with a post-sternum AA diagnosis ( P=0.005) . Patients with ICUS/CCUS showed no difference in OS compared with AA and hypo-MDS ( P=0.095 and P=0.480, respectively) . A 4-item predictive scoring system to identify hypocellular BMFS patients that need sternal bone marrow evaluation was developed, including age > 60 years old ( OR=6.647, 95% CI 1.954-22.611, P=0.002, 2 points) , neutrophil alkaline phosphatase score ≤ 160 ( OR=2.654, 95% CI 1.214-5.804, P=0.014, 1 point) , abnormal erythroid markers evaluated by flow cytometry on iliac bone marrow ( OR=6.200, 95% CI 1.165-32.988, P=0.032, 2 points) , and DAT (DNMT3A, ASXL1, TET2) genes mutation ( OR=4.809, 95% CI 1.587-14.572, P=0.005, 1 point) . The Akaike information criterin (AIC) was 186.1. Conclusion:Patients with a pre-sternum acquired hypocellular BMFS diagnosis characterized by normal cytogenetics may not reach accurate diagnostic categorization without sternal bone marrow cell morphology evaluation, which could be considered a diagnostic tool for this patient population. A predictive scoring system was developed, and when the total score is ≥ 2 points, sternal bone marrow evaluation should be performed for accurate diagnostic categorization that is critical to optimal patient care.

Objective:To explore the genetic characteristics, clinical features, and prognostic values of RAS mutations in patients with myelofibrosis (MF) .Methods:We analyzed 112-gene targeted sequencing data from 226 patients who had a diagnosis of either primary myelofibrosis (PMF) or post-polycythemia vera/post-essential thrombocythemia (post-PV MF and post-ET MF) from December 2011 to December 2019. A retrospective analysis of the genetic characteristics, clinical features, and prognosis of RAS mutations was performed.Results:Among 266 patients diagnosed PMF or post-PV/ET MF, RAS mutations were found in 14 (6.2%) cases, including 9 (4.0%) cases of NRAS mutations, 8 (3.5%) cases of KRAS mutations, and 3 (1.3%) cases of both NRAS and KRAS mutations. All of the NRAS mutations were located in codons 12 and 13. The median VAFs of RAS mutations were significantly lower than those of the driver mutations, confirming that they represent sub-clonal events that are acquired during the disease course. SETBP1, SRSF2, and MPL tended to be clustered with RAS mutations. Patients with RAS mutations had a higher number of additional oncogenic mutations (median, 3.36 vs 1.17, P<0.001) . RAS mutations had a statistically significant association with elevated monocyte cell counts ( P=0.003) , lower platelet counts ( P=0.026) , higher bone marrow blasts ( P=0.022) , splenomegaly ( P=0.005) , and very high-risk (VHR) karyotype abnormality percentage ( P=0.031) . In univariate analysis, the OS of patients with NRAS mutations were significantly inferior in the entire MF and PMF cohorts ( P=0.001, P=0.008) . In a multivariate model, NRAS retained an independent negative prognostic factor in PMF. Conclusion:RAS gene mutations were constantly related to elevated monocyte cell counts, lower platelet counts, higher bone marrow blasts, and VHR karyotype abnormality percentage that usually defined high-risk disease and often occurred as sub-clonal events. NRAS mutation is an independent poor prognostic factor in PMF.

Objective To detect the serum level of 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF),a significant metabolite offish oil,in subjects with normal glucose tolerance (NGT) in local communities,and to investigate the association of CMPF with fatty acid metabolism.Methods A total of 272 NGT participants from screening for diabetes in Shanghai in 2013 were enrolled.Anthropometric measurements,biochemical evaluation,and questionnaire interview were performed for all the participants.The participants were divided into normal weight group [body mass index (BMI) ≤23.9 kg/m2,n =143] and overweight/obesity group (BMI ≥ 24 kg/m2,n =129).The serum CMPF concentrations were determined using an enzyme-linked immunosorbent assay.Results Serum CMPF level in overweight/obesity group was lower than that in normal weight group [96.50 (46.11,169.56) μmol/L vs 153.20 (83.16,282.97) μmol/L,P＜0.05].The serum CMPF level was negatively correlated with BMI (r =-0.256,P＜0.01),triglycerides (r =-0.175,P =0.004),and free fatty acid (r =-0.126,P =0.041) according to bivariate correlation analyses.A multivariate stepwise linear regression analysis showed that the serum CMPF level was independently associated with BMI,triglycerides,free fatty acid,and HbA1C.A logistic regression analysis showed that the CMPF was a protective factor against obesity (OR =0.324,95％ CI 0.158,0.664).Conclusion Serum CMPF level is reduced in overweight/obese subjects.CMPF is beneficial to lipid metabolism.