BACKGROUND:Precision therapy based on multifunctional nanomaterials is a novel therapeutic model for malignancies that can integrate multiple imaging and therapeutic models into one nanoscale platform to achieve visual combination treatment. OBJECTIVE:To prepare novel nanoparticles loaded with Cu2(OH)PO4 nanoparticles(CuNPs)and nuciferine(NF)(h-PCuNF),and to explore their ability to mediate combined photothermal therapy/photodynamic therapy/chemodynamic therapy/chemotherapy for malignancy. METHODS:The h-PCuNF nanoparticles were synthesized through a double-emulsion procedure,through which the CuNPs and NF were loaded into the shell of hollow poly(lactic-co-glycolic)acid nanocarriers.The morphology,structure,particle size,and zeta potential of the h-PCuNF nanoparticles were characterized.In deionized water,the magnetic resonance imaging and photothermal conversion performances of the h-PCuNF nanoparticles,as well as their capability to implement reactive oxygen species production by mediating photocatalysis and Fenton-like reactions,were evaluated.In liver malignant tumor cell line HepG2 cells,the effectiveness of the photothermal therapy/photodynamic therapy/chemodynamic therapy/chemotherapy combination therapy mediated by the nanoparticles was detected by employing fluorescence imaging and MTT assay. RESULTS AND CONCLUSION:(1)The h-PCuNF nanoparticles possessed a hollow spherical structure in which the CuNPs(drug loading rate and encapsulation rate were 26.3%and 63.2%,respectively)and NF(drug loading rate and encapsulation rate were 11.0%and 52.6%,respectively)were loaded into the shell.The average particle size of the h-PCuNF nanoparticles was(309.2±10.0)nm,while the zeta potential was determined to be(-12.5±0.9)mV.In physiological environments,the nanoparticles possess favorable suspension stability.(2)In deionized water,the h-PCuNF nanoparticles could markedly enhance T1-weighted magnetic resonance imaging images.The h-PCuNF nanoparticles showed remarkable photothermal conversion and photocatalytic reactive oxygen species generation capabilities under near infrared laser irradiation.In addition,the h-PCuNF nanoparticles could consume glutathione and mediate Fenton-like reactions to produce·OH.(3)The h-PCuNF nanoparticles could be taken up by HepG2 tumor cells and were mainly distributed in the cytoplasm.The synergistic therapeutic effect was demonstrated after the nanoparticles were activated by near infrared laser irradiation,because CuNPs mediated photothermal therapy/photodynamic therapy/chemodynamic therapy and NF mediated chemotherapy could synergistically eliminate the tumor cells.

Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.

Objective:To evaluate the clinical outcomes of combined complete preservation of chordal structure mitral valve replacement (C-MVR) with total anatomical arterial myocardial revascularization (TACR) in coronary patients with moderate-to-severe or severe ischemic mitral regurgitation (IMR).Methods:This is a retrospective multi-center case series study. Data were retrospectively collected from 127 patients with coronary artery disease with moderate to severe or severe IMR who received TACR with C-MVR from July 2015 to April 2024 in 13 hospitals in China. There were 90 males and 37 females, aged (56.5±10.7) years (range: 33 to 74 years). Perioperative data and follow-up data including left ventricular ejection fraction, left ventricular end-diastolic diameter, and patency rate of arterial grafts of patients were collected. Comparisons were made using paired sample t-test or χ2 test. Results:In this cohort of 127 patients, 67 underwent concurrent tricuspid valve repair. During surgery, 113 grafts of the left internal mammary artery (LIMA), 127 grafts of the left radial artery, 80 grafts of the right radial artery, and 110 grafts of the right internal mammary artery (RIMA) were harvested. The number of the distal anastomosis was 4.2±0.4 (range: 3 to 5). The aortic cross-clamp time and cardiopulmonary bypass time were (97.5±23.4) minutes (range: 90 to 161 minutes) and (145.4±19.2) minutes (range: 101 to 210 minutes), respectively. There was one operative death. Intraoperative placement of an intra-aortic balloon pump was performed in 21 patients to improve the left ventricular ejection. No sternal ischemic occurred. All patients completed follow-up, with a mean follow-up period of (64.3±7.5) months (range: 4 to 110 months). No major cerebrovascular events occurred during the follow-up period, and all patients survived. Left ventricular ejection fraction improved postoperatively (55.0%±5.3% vs. 41.0%±15.3%, t=17.23, P<0.01). The proportion of patients with New York Heart Association functional class ≤2 increased postoperatively (23.6% (30/127) vs. 87.3% (110/126), χ2=103.77, P<0.01). The proportion of patients with Canadian Cardiovascular Society Angina Classification ≤3 decreased postoperatively (4.8% (6/126) vs. 78.7% (100/127), χ2=142.19, P<0.01). The left ventricular end-diastolic diameter decreased postoperatively ((5.70±4.50) cm vs. (6.10±0.23) cm, t=12.15, P<0.01). Coronary multi-detector computed tomography angiography (MDCTA) follow-up was conducted for (60.5±11.7) months (range: 6 to 109 months) postoperatively. MDCTA confirmed the patency rates of the grafts: 96.4% (108/112) for the LIMA grafts, 88.9% (112/126) for the left radial artery grafts, 93.7% (74/79) for the right radial artery grafts, and 90.9% (100/110) for the free RIMA grafts. No significant differences in graft patency rates were observed between the arterial grafts ( χ2=5.24, P=0.155). Conclusion:The results of this multi-centre study demonstrate satisfactory mid-term results of C-MVR with TACR for the treatment of coronary artery disease with moderate to severe or severe IMR.

Objective To explore the relationship between ultrasonographic characteristics and promoting angiogenesis related genes in breast invasive ductal carcinoma.Methods A search was conducted in the PubMed database to identify genes related to promoting an-giogenesis in breast cancer.Protein-protein interaction networks(PPI)were constructed using the STRING database and Cytoscape soft-ware,and screen for key genes.A total of 38 female patients diagnosed with breast invasive ductal carcinoma from January 2022 to August 2023 were included in the study.The relationship between clinical and ultrasonographic characteristics of these patients and key genes was analyzed.Results A total of 10 key genes were screened.The expression levels of TGF-β1 and CXCL12 in patients aged＞50 years were higher than those in patients aged ≤50 years(P＜0.05).The expression level of IL-6 in patients with lymph node metastasis was higher than that in patients without lymph node metastasis(P＜0.05).The expression level of CCL2 in patients with color pixel percent-age(CPP)of ultra micro angiography(UMA)＞10％was higher than that in patients with CPP of UMA ≤10％(P＜0.05).The ex-pression level of Akt1 in patients with predominantly peripheral vascular distribution were higher than that in patients with central distribu-tion(P＜0.05).The expression levels of IL-6,TGF-β1,PEC AM1,CXCL8 and CXCL12 in patients with uneven contrast perfusion were higher than those in patients with even contrast perfusion(P＜0.05).The expression levels of TGF-β1,PEC AM1,FN1 and CX-CL12 in patients with contrast perfusion defect area＞1/2 were higher than those in patients with contrast perfusion defect area≤1/2(P＜0.05).There was a correlation among genes involved in regulating contrast perfusion uniformity and perfusion defect area,particu-larly the intersecting genes TGF-β1,PECAM1 and CXCL12(P＜0.05).Conclusion There is a correlation between the ultrasono-graphic characteristics of breast invasive ductal carcinoma and key genes related to promoting angiogenesis,which may provide a reference for individualized treatment of breast cancer.

Objective:To compare the results of operative versus interventional treatments in patients presenting with sentinel hemorrhage after hepatobiliary and pancreatic surgery.Methods:The clinical data of patients presenting with sentinel hemorrhage after hepatobiliary and pancreatic surgery at the Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Guangzhou Medical University from August 2017 to July 2022 were retrospectively analyzed. Of 82 patients who were enrolled in this study, there were 50 males and 32 females, aged (59.0±7.7) years. The patients were divided into the interventional group ( n=42) and the surgical group ( n=40) based on the treatment they received for sentinel hemorrhage. The vascular injury rate, the first operation time for sentinel bleeding, the rate of successful hemostasis in a single operation, the number of deaths and other indicators were compared between groups. Results:In both the two groups of patients who underwent percutaneous transhepatic cholangial drainage, hepatectomy, endoscopic retrograde cholangiopancreatography, hilar cholangiocarcinoma resection and cholecystectomy were mainly performed hepatic artery injury, pancreaticoduodenectomy with gastroduodenal artery injury, and splenectomy with splenic artery injury. In the intervention group, 36 patients (85.7%) were successfully hemostasis after single treatment, and 32 patients (80.0%) in the operation group, and there was no significant difference between the two groups (χ 2=0.47, P=0.492). The first operation time for the intervention group was (40.5±8.5) min and the mortality rate was 2.4% (1/42), which were significantly better than that of the operation group (90.6±20.8) min and 15.0% (6/40) (all P<0.05). Conclusion:Interventional therapy can be used as the first-line diagnosis and treatment for sentinel bleeding after hepatobiliary and pancreatic surgery. It has the advantages of a lower mortality rate in treating these patients.

Objective:To verify the prognostic significance of the tumor regression grade (TRG) for muscle-invasive bladder cancer (MIBC) patients undergoing radical cystectomy (RC) after neoadjuvant chemotherapy.Methods:The data of 70 MIBC patients treated with gemcitabine combined with cisplatin neoadjuvant chemotherapy and RC in Sun Yat-sen University Cancer Center between July 2016 to November 2021 were retrospectively reviewed. There were 65 males and 5 females, with an average age(59.79±10.56)years old. The patients accepted transurethral resection of bladder tumor (TURBT) specimens before neoadjuvant chemotherapy. Clinicopathological characteristics of patients were recorded and TRG was assessed. TRG evaluation criteria: TRG 1 was defined as no cancer residue, TRG 2 was defined as the proportion of residual cancer area to tumor bed area <50%, and TRG 3 was defined as the proportion of residual cancer area to the area of the tumor bed ≥ 50%. Chi-square test or Fisher's exact test were used to compare the relationship between patients' clinicopathological characteristics and TRG. The relationship between post-neoadjuvant therapy tumor and node(ypTN)stage, and survival, including overall survival(OS)and recurrence-free survival (RFS) were analyzed by Kaplan-Meier analysis. The pathologically locally descending disease was defined as (ypT < T 2 and ypN=N 0) and pathologically locally advanced disease was defined as (ypT≥T 2 and/or ypN ≥N 1). Cox regression was used for univariate and multivariate analysis of OS and RFS. Results:Chi-square test or Fisher exact test analysis showed TRG was significantly associated with ypT stage ( P < 0.001), ypN stage ( P = 0.002), lympho-vascular invasion ( P<0.001) and variant histology ( P<0.001). The OS of patients with TRG 1, TRG 2 and TRG 3 were 20.5(10.3, 31.8), 17.0(11.0, 30.8)and 15.0(11.0, 26.0) months, respectively, and the difference was significantly different( P = 0.037). The RFS of patients with TRG 1, TRG 2 and TRG 3 were 15.0(8.3, 25.5), 15.0(8.0, 27.0)and 11.0(4.5, 25.5) months, respectively, and the difference was significantly different ( P=0.029). There were significant differences between patients with pathologically locally descending disease and locally advanced disease in OS [18.5(10.3, 30.8)vs.15.0(11.0, 27.3)months, P = 0.013] and RFS [14.0(8.0, 24.0)vs. 11.5(8.0, 26.8)months, P = 0.012]. Among patients with locally advanced pathology, the OS was 19.5(11.0, 32.5)months for patients with TRG ≤2, 13.5(10.8, 26.0)months for patients with TRG 3( P=0.140). The RFS was 12.0(8.0, 31.0)months for those patients with TRG ≤2 and 11.0(6.0, 26.0)months for those patients with TRG 3( P = 0.180). Cox univariate analyses showed that patients with TRG 3 were associated with decreased OS ( HR = 6.043, 95% CI 1.170-31.213, P = 0.032) and RFS ( HR = 6.354, 95% CI 1.231-31.802, P = 0.027). Conclusions:This study showed that TRG was correlated with OS and RFS among patients. The patients who had the higher TRG had the worse prognosis. It was confirmed that TRG predicted the prognosis of patients undergoing radical cystectomy after neoadjuvant chemotherapy. Therefore, TRG assessment is recommend in pathology report for patients who had radical cystectomy after neoadjuvant chemotherapy.

Objective:To analyze the clinicopathological characteristics of differentiated early cardia cancer and to evaluate the short-term and long-term efficacy of endoscopic submucosal dissection (ESD).Methods:A total of 329 patients (331 lesions) who underwent ESD at Nanjing Drum Tower Hospital from October 2014 to December 2019 and were pathologically confirmed as differentiated early cardia cancer were included in the study and followed up. The endoscopic and pathological data of patients were reviewed to analyze the clinicopathological characteristics of differentiated early cardia cancer. The short-term (including en bloc resection rate, curative resection rate and incidence of short-term complications) and long-term efficacy (including incidence of metachronous cancer, recurrence and distant metastasis, and overall survival rate) of ESD was evaluated.Results:The ratio of male to female in 329 patients with differentiated early cardia cancer was 4∶1, and their age was 65.69±8.02 years. Tumor diameter of ≤2.0 cm accounted for 65.9% (218/331). Most lesions were located on the posterior wall (50.5%, 167/331), followed by the minor curve (36.3%, 120/331). The endoscopic morphology of 0-Ⅱc type accounted for 49.5% (164/331). There were 69.8% (231/331) lesions confined to the mucosal layer. The en bloc resection rate was 100.0% (329/329), and the curative resection rate was 83.3% (274/329). Short-term complications occurred in 28 patients (8.5%). With a median follow-up time of 39 months, 11 patients (3.3%) developed metachronous cancer, 2 (0.6%) developed distant metastasis, and no recurrence occurred. Seven patients died, and the overall survival rate during the follow-up period was 97.9% (322/329). The survival rate of patients with curative resection and additional surgery was 100.0% (3/3), while that without additional surgery was 99.3% (269/271). The survival rate of patients with non-curative resection and additional surgery was 96.0% (24/25), and that without additional surgery was 86.7% (26/30).Conclusion:Most differentiated early cardia cancers are well-differentiated adenocarcinomas, with less than 2 cm in diameter at the time of diagnosis with a low rate of ulcer and vascular invasion. ESD is safe and effective for the treatment of differentiated early cardia cancer with a high rate of curative resection, fewer intraoperative and postoperative complications, low incidences of metachronous cancer, distant metastasis and recurrence, and a high overall survival rate. However, additional surgical treatment is recommended for patients with non-curative resection.

Antibodies, Neutralizing ; Antibodies, Viral/isolation & purification* ; B-Lymphocytes/virology* ; COVID-19/virology* ; Humans ; Immunity/genetics* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Single-Cell Analysis

Objective:To study the safety and efficacy of endoscopic submucosal dissection (ESD) for early gastric cardia cancer (EGCC) in elderly patients.Methods:A retrospective analysis was performed on data of 499 EGCC patients who underwent ESD from January 2011 to June 2018 in Nanjing Drum Tower Hospital. The patients were divided into two groups by age, the young/middle-aged group (<65 years old) and the elderly group (≥65 years old). The baseline data, lesion features, postoperative complications, short-term efficacy and long-term efficacy of the two groups were compared.Results:The elderly group included 272 patients (283 lesions) and the young/middle-aged group included 227 patients (229 lesions). Except that there were significant differences in the age ( P<0.001) and body mass index ( P=0.002) between the elderly group and the young/middle-aged group, there were no significant differences in the baseline data or pathological features between the two groups. The rate of curative resection in the elderly group was 77.0%, lower than that in the young/middle-aged group (84.3%, P=0.045). No significant differences were found in en bloc resection rate (100.0% VS 99.6%, P=1.000), complete resection rate (94.7% VS 93.9%, P=0.705), postoperative complications incidence (6.4% VS 5.7%, P=0.747), operation time (64.02±39.24 min VS 66.16±44.62 min, P=0.566) or hospitalization time (6.76±2.06 d VS 6.47±1.74 d, P=0.092]. After the median follow-up of 47.9 months, 13.4% patients in the elderly group received additional surgery, which was slightly lower than that in the young/middle-aged group ( P=0.891). There were no significant differences in postoperative recurrence, lymph node metastasis, distant metastasis, overall mortality and disease-related mortality between the two groups. The survival analysis showed that five-year overall survival rates were 94.41% and 96.34% in the elderly group and the young/middle-aged group respectively ( P=0.156), and five-year disease-specific survival rate were 99.18% and 99.03% in the two groups respectively ( P=0.858). Conclusion:ESD is safe and effective for EGCC in elderly patients with satisfactory short-term and long-term efficacy.

Objective:Continuous acquisition of swallowing images of head and neck cancer patients by using MRI technique was performed to observe and measure the movement regularity and maximum displacement of the soft palate, tongue and larynx.Methods:From July 2018 to October 2018, 20 patients with primary head and neck cancer were chosen randomly, 17 male and 3 female. The median age was 58.5 years (28 to 78 years). Among the 20 patients, 7 patients were diagnosed with nasopharyngeal carcinoma, 3 patients with oral cancer, 5 patients with oropharyngeal cancer, 3 patients with hypopharyngeal cancer, and 2 patients with nasal and paranasal sinuses cancer. Two patients were classified as stage Ⅰ-Ⅱ, 8 patients as stage Ⅲ and 10 patients as stage Ⅳ according to the eighth edition of AJCC.Results:The displacement of the upward movement of the soft palate during swallowing was (1.06±0.31) cm and followed the pattern normal distribution. The displacement of backward movement of the soft palate was (0.83±0.24) cm, which also almost normally distributed. The displacement of backward tongue movement was (0.77±0.22) cm and followed the normal distribution pattern. The displacement of upward tongue movement was 0 in patients with tongue depressor for image acquisition. The mediandisplacement of upward tongue movement in patients without tongue depressor was 1.23 cm (0.59 to 1.41 cm). The displacement of upward laryngeal movement was (1.14±0.22) cm and followed the normal distribution pattern, and the median displacement of forward laryngeal movement was 0.4 cm (0.27 to 0.90 cm).Conclusions:Swallowing movement may occur in head and neck cancer patients during radiotherapy. It can also cause the movement of gross tumor volume (GTV) and surrounding normal tissues. Therefore, extensive attention should be paid to the individual distance between GTV and planning gross tumor volume (PGTV) when making radiotherapy plans, aiming to ensure the prescription dose of cancer.