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 explore the efficacy of transcystoscopic holmium laser sieve-shaped fenestration in the treatment of ureteral cysts in children. Methods: The clinical data of 41 children with ureteral cysts treated in our hospital during Jan.2019 and Dec.2023 were retrospectively analyzed.All children received this surgery.The perioperative indicators and postoperative outcomes were recorded. Results: All operations were successful, the average operation time being (32.20±11.49) min.During the 12-month follow-up, the cysts were reduced or the obstructive symptoms were relieved in 31 cases, and the cysts completely disappeared in 6 cases.Vesicoureteral reflux (VUR) developed in 4 cases, 1 of which had grade Ⅱ VUR with no obvious symptoms and received conservative treatment.Repeated urinary tract infections developed in 2 cases; obstructive symptoms remained unchanged in 1 case; these 3 cases received vesicoureteral replantation.Two days before operation and 3 months after operation, the ureter diameter was (9.95±2.38) mm and (7.41±3.39) mm (t=3.16, P＜0.05), the anteroposterior diameter of the renal pelvis was (13.32±2.63) mm and (9.07±3.02) mm (t=6.86, P＜0.01). Conclusion: Transcystoscopic holmium laser sieve-shaped fenestration for children with ureteral cysts has good efficacy, little trauma and few complications.It can quickly relieve obstructive symptoms and can be used as the initial treatment of ureteral cysts.

ObjectiveTo explore the potential mechanism of different processed products of Baiyaojian and its compound Xiangmei pills in rats with ulcerative colitis（UC） by comparing the pharmacodynamic and metabolomic differences. MethodEighty SD rats were acclimatized and kept for 3 d， and randomly divided into 8 groups［blank group， model group， mesalazine group（0.4 g·kg^-1）， Baiyaojian group（1.89 g·kg^-1）， stir-fried Baiyaojian group（1.89 g·kg^-1）， carbonized Baiyaojian group（1.89 g·kg^-1）， and Xiangmei pills low and high dose groups（1.89， 5.67 g·kg^-1）］， with 10 rats in each group. Rats in the blank group were administered physiological saline by gavage， and rats in the remaining 7 groups were orally administered 5% dextran sodium sulfate（DSS） solution daily for 8 consecutive days to induce UC model. After successful modeling， each dosing group was given the corresponding dose of drug solution by gavage， and the blank and model groups were given equal amounts of saline by gavage， and the drug was administered continuously for 8 d. Then serum levels of tumor necrosis factor-α（TNF-α）， interleukin（IL）-6， IL-10 and IL-1β were measured by enzyme-linked immunosorbent assay（ELISA）， hematoxylin-eosin（HE） staining was used to observe the histopathological changes of colon tissue， the proportion of T helper 17 cells（Th17） and regulatory T cells（Treg） in the peripheral blood of rats in each group was detected by flow cytometry. The endogenous metabolites in serum of rats were detected by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites were characterized by combining principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， and were analyzed according to the variable importance in the projection（VIP） value>1.0 and P<0.05， and potential metabolic pathways were analyzed according to Human Metabolome Database（HMDB）. ResultCompared with the blank group， the colon tissue of the model group was congested and the mucosa was ulcerated， the colon length was significantly reduced（P<0.01） and the quality was significantly increased（P<0.05）， the proportion of Th17/Treg in the peripheral blood and the serum levels of TNF-α， IL-6 and IL-1β were significantly increased， while the IL-10 expression wassignificantly reduced（P<0.05， P<0.01）. Compared with the model group， the colon tissue of UC rats in each treatment group was improved with scattered ulcers， reduced inflammatory cell infiltration， significantly increased colon length， and significantly decreased mass（P<0.05）， the proportion of Th17/Treg in the peripheral blood decreased， the expression of TNF-α，IL-6 and IL-1β was significantly reduced（P<0.05， P<0.01）， while the IL-10 expression was significantly increased（P<0.01）. The therapeutic effect of different administration groups on UC was in the order of high dose group of Xiangmei pills>low dose group of Xiangmei pills>carbonized Baiyaojian group>stir-fried Baiyaojian group>Baiyaojian group. And a total of 26 differential metabolites were screened in the metabolomics results. Compared with the blank group， 14 differential metabolites were up-regulated and 5 metabolites were down-regulated in the model group， and 14， 9， 14， 12 and 17 metabolites could be recalled in the Baiyaojian group， stir-fried Baiyaojian group， carbonized Baiyaojian group， Xiangmei pills low and high dose groups. The main metabolic pathways involved were citrate cycle pathway， pantothenic acid and coenzyme A biosynthesis pathway， aromatic hydrocarbon receptor（AhR） signaling pathway， glycolysis/gluconeogenesis pathway. ConclusionThe therapeutic effect of Baiyaojian on UC is significantly improved after charcoal stir-frying， and the efficacy is more prominent when combined with Angelicae Dahuricae Radix and Mume Fructus Carbonisata， which can provide a basis for the development of Baiyaojian compound preparations.

Objective:To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma.Methods:This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People′s Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method.Results:Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95% CI:93.4% to 100%) and 90.7%(95% CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95% CI:83.0% to 99.8%) and 71.3%(95% CI:58.7% to 86.5%). Conclusions:The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

Objective:To investigate the value of three-dimensional (3D) T 1WI structural images using different acceleration methods including parallel acquisition technique, joint compressed sensing (uCS) technique, and artificial intelligence-assisted compressed sensing (ACS) technique for brain region segmentation. Methods:In this cross-sectional study, fifty patients (female: n=25, age range: 13 to 87 years old) at Corning Hospital of Ningbo University from July to September 2023 were prospectively and consecutively collected. All the subjects underwent brain MRI. Six groups of 3D T 1WI structural images were obtained using different acceleration technique and parameters, including 3D T 1WI without acceleration factor (3D-T 1WI group), 3D T 1WI with parallel acquisition technique with acceleration factor 3 (3D-T 1WI-PI-3 group), 3D T 1WI with uCS technique with acceleration factor 4.5 and 6.9 (3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group), 3D T 1WI by ACS technique with acceleration factors of 3 and 5 (3D-T 1WI-ACS-3 group, 3D-T 1WI-ACS-5 group). T 2WI fluid-attenuated inversion recovery (FLAIR) images were also acquired. Subjective scores (cerebral grey matter and white matter clarity scores, clarity scores of cerebral white matter degeneration lesions in relation to the surrounding white matter, and Gibbs artifact scores) and objective metrics [signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), cerebrospinal fluid signal homogeneity, peak signal-to-noise ratio (PSNR), structural similarity index (SSIM), and natural image quality evaluator (NIQE)] were used to evaluate image quality in different groups. Totally 109 brain regions were segmented and volumes were measured using the uAI Research Portal image analysis tool. Kappa or intraclass correlation coefficient ( ICC) was used to evaluate the agreement of subjective and objective evaluation indexes between the 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group, 3D-T 1WI-ACS-3 group, 3D-T 1WI-ACS-5 group, and 3D-T 1WI group. Kappa or ICC value>0.70 was considered as good agreement. Results:The acquisition time for the 3D-T 1WI group, 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group, 3D-T 1WI-ACS-3 group, and 3D-T 1WI-ACS-5 group were 527, 204, 169, 95, 133, 90 s, respectively. Subjective evaluation showed that the 3D-T 1WI-uCS-4.5, 3D-T 1WI-ACS-3, and 3D-T 1WI-ACS-5 groups had excellent agreement with the 3D-T 1WI group in terms of the distribution of cases of cerebral grey matter and white matter clarity scores, respectively (all Kappa value=1.000); The distribution of cases of clarity score of cerebral white matter lesions and surrounding white matter in the 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, and 3D-T 1WI-ACS-3 group were in good agreement with that of the 3D-T 1WI group ( Kappa values of 0.775, 0.701, and 0.777, respectively); the distribution of the number of cases of the Gibbs artifact score of the 3D-T 1WI-uCS-4.5, 3D-T 1WI-ACS-3, and 3D-T 1WI-ACS-5 groups was in good agreement with the 3D-T 1WI group (all Kappa value=1.000). Objective evaluation showed the CNR of the images in the 3D-T 1WI-PI-3, 3D-T 1WI-uCS-4.5, and 3D-T 1WI-uCS-6.9 groups were in good agreement with those of the 3D-T 1WI group ( ICC of 0.720, 0.759, and 0.752, respectively); PSNR and SSIM were in good agreement among the 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, 3D-T 1WI-uCS-6.9 group, 3D-T 1WI-ACS-3 group, and 3D-T 1WI-ACS-5 group (PSNR: ICC=0.854; SSIM: ICC=0.851). NIQE of 3D-T 1WI-PI-3 group, 3D-T 1WI-uCS-4.5 group, and 3D-T 1WI-ACS-3 group images were in good agreement with the 3D-T 1WI group ( ICC value of 0.866, 0.727, 0.753, respectively). The ICC values of the volume of each segmented brain region among the 3D-T 1WI-PI-3, 3D-T 1WI-uCS-4.5, 3D-T 1WI-uCS-6.9, 3D-T 1WI-ACS-3, 3D-T 1WI-ACS-5 group and the 3D-T 1WI group images showed decreased in order (all ICC≥0.62). Conclusions:The uCS and ACS techniques used in 3D-T 1WI show high agreement with 3D-T 1WI in terms of brain segmentation. The application of these accelerating techniques can significantly shorten the acquisition time with obtaining images with good image quality, displaying great value.

Objective:To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma.Methods:This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People′s Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method.Results:Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95% CI:93.4% to 100%) and 90.7%(95% CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95% CI:83.0% to 99.8%) and 71.3%(95% CI:58.7% to 86.5%). Conclusions:The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

Objective To investigate the risk factors associated with necrosis in interstitial oedematous pancreatitis(IOP)and to develop a nomogram model for the early prediction of necrosis in IOP.Methods A retrospective analysis was conducted on 306 patients diagnosed with IOP.Patients were stratified into necrosis and edema groups based on the presence or absence of pancreatic necrosis through follow-up CT-enhanced examinations.Logistic regression analysis was employed to identify independent predictive factors for necrosis in IOP.Subsequently,a nomogram model was developed,and its discriminative ability,accuracy,and practicality were assessed through receiver operating characteristic(ROC)curve,calibration curve,and decision curve analysis(DCA).Results Balthazar computed tomography severity index(CTSI),gender,lactate dehydrogenase(LDH),and triglyceride(TG)were finally identified as four independent predictors for constructing the nomogram model.The area under the curve(AUC)of the nomogram model was 0.800[95％confidence interval(CI)0.731-0.869].The calibration curve indicated good consistency between the predicted probabil-ity and the actual probability of necrosis in IOP(P=0.737).DCA suggested high practicality of the nomogram model within the threshold probability range of 3％to 66％and 75％to 96％.Conclusion The nomogram model based on Balthazar CTSI,gender,LDH,and TG demonstrates good efficacy in early prediction of necrosis in IOP.

The mechanisms of the chronic pain and depression comorbidity have gained significant attention in recent years. The complement system, widely involved in central nervous system diseases and mediating non-specific immune mechanisms in the body, remains incompletely understood in its involvement in the comorbidity mechanisms of chronic pain and depression. This review aims to consolidate the findings from recent studies on the complement system in chronic pain and depression, proposing that it may serve as a promising shared therapeutic target for both conditions. Complement proteins C1q, C3, C5, as well as their cleavage products C3a and C5a, along with the associated receptors C3aR, CR3, and C5aR, are believed to have significant implications in the comorbid mechanism. The primary potential mechanisms encompass the involvement of the complement cascade C1q/C3-CR3 in the activation of microglia and synaptic pruning in the amygdala and hippocampus, the role of complement cascade C3/C3a-C3aR in the interaction between astrocytes and microglia, leading to synaptic pruning, and the C3a-C3aR axis and C5a-C5aR axis to trigger inflammation within the central nervous system. We focus on studies on the role of the complement system in the comorbid mechanisms of chronic pain and depression.

Stigma can lead to social isolation, poor therapeutic compliance, and decreased quality of life in patients with maintenance hemodialysis. This paper reviewed literatures from both domestic and international sources, focusing on five aspects pertaining to the origins, harms, assessment tools, influencing factors, and intervention measures of perceived stigma in patients with maintenance hemodialysis, in order to provide theoretical grounding and serve as a reference for conducting related researches and implementing domestic nursing interventions.

Objective:To assess the clinical efficacy of sequential radical surgery after immune and targeted therapy in downstaging patients with initially unresectable hepatocellular carcinoma.Methods:Data were prospectively collected from December 2018 to July 2022 on patients with initially unresectable hepatocellular carcinoma which were downstaged to undergo sequential surgery after treatment with immune and targeted therapy at the Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital. There were 79 patients, with 69 men and 10 women, aged (53.0±10.9) years, being enrolled into this study. The Kaplan-Meier method was used to calculate the survival rate, and the log-rank test was used for survival rate comparison. Univariate and multivariate Cox regression were used to analyze factors influencing patient prognosis.Results:There were 7 patients (8.9%) with China Liver Cancer Staging (CNLC) Ⅰb, Ⅱa, Ⅱb who had insufficient residual liver volume or tumor rupture before the downstaging therapy, and 38 patients (48.1%) with CNLC Ⅲa and 34 patients (43.0%) with CNLC Ⅲb. These 79 patients underwent R 0 resection after 3-20 cycles (median 5 cycles) of immune and targeted therapy. Based on the modified response evaluation criteria in solid tumor, the results of preoperative imaging assessment were: complete remission in 12 patients (15.2%), partial remission in 50 patients (63.3%), stable disease in 15 patients (19.0%), and disease progression in 2 patients (2.5%). The overall survival rates of patients at 1, 2, and 3 years after diagnosis were 96.1%, 83.5%, and 76.6%; and the recurrence-free survival rates at 1, 2, and 3 years after surgery were 62.1%, 52.9%, and 34.7%, respectively. On multivariate Cox regression analysis, patients with a preoperative alpha-fetoprotein >20 μg/L ( HR=2.816, 95% CI: 1.232-6.432, P=0.014) and a high proportion of pathological residual tumors ( HR=1.015, 95% CI: 1.004-1.026, P=0.006) had a higher risk of postoperative recurrence; and patients with a high proportion of pathological residual tumors ( HR=1.028, 95% CI: 1.007-1.049, P=0.007) and preoperative alpha-fetoprotein >400 μg/L ( HR=4.099, 95% CI: 1.193-14.076, P=0.025) had a higher risk of death. Conclusion:Immunotherapy combined with targeted therapy and sequential surgery for patients with initially unresectable hepatocellular carcinoma provided long-term survival benefits. Elevated preoperative alpha-fetoprotein and a high proportion of pathological residual tumor were independent risk factors for recurrence-free survival and overall survival in this group of patients.