Hepatocellular carcinoma (HCC) has an insidious onset and high malignancy. Most patients have progressed to intermediate and advanced stages by the time of diagnosis, and the long-term efficacy of ...traditional treatments is not satisfactory. Immunotherapy has shown great promise in the treatment of HCC in recent years; however, the low immunogenicity and severe immunosuppressive tumor microenvironment result in a low response rate to immunotherapy in HCC patients. Therefore, it is of great significance to improve the immunogenicity of HCC and thus enhance its sensitivity to immunotherapy. Here, we prepared the boronophenylalanine-modified dual drug-loaded polydopamine nanoparticles by a facile method. This system used boronophenylalanine-modified polydopamine nanoparticles as a delivery vehicle and photothermal material for the chemotherapeutic drug doxorubicin and the immune agonist CpG oligodeoxynucleotides (CpG-ODN), with both active targeting and lysosomal escape functions. The cancer cells are rapidly killed by photothermal treatment, and then chemotherapy is used to further kill cancer cells that are inadequately treated by photothermal treatment. The combination of photothermal-chemotherapy synergistically induces the release of relevant antigens from tumor cells, thus initiating anti-tumor immunity; and then cooperates with CpG-ODN to trigger a powerful anti-tumor immune memory effect, potently and durably inhibiting HCC recurrence.
Coal spontaneous combustion significantly threatens the mine production safety. This paper focuses on the practical aspects of the disaster within the sealed goaf of Pingmei No. 11 mine. Obtained the ...characteristic parameters of spontaneous combustion in goaf by arranging high-level drilling field and drilling method. The grey correlation analysis method was applied to analyze the determination index of the effective characterization of the hidden spontaneous combustion area range, and interpolation aided in assessing these indicators before and after the increase amount of N2 injection. All showed that the hidden spontaneous combustion area was determined to be 70–80 m away from the return air side and 10–15 m away from the stop line, and the comprehensive treatment technologies are executed to control the spontaneous combustion hazards, including injecting inert gas to cool the high-temperature area, injecting the aqueous foam to cover the fire source, and plugging leakage to isolation the O2. Finally, the O2 concentration in goaf dropped below 5.0%, and carbon monoxide concentration fell below 0.001% after implementing these methods, effectively controlling the coal spontaneous combustion disaster. The successful management of concealed coal spontaneous combustion disasters offers a valuable reference for identifying and efficiently addressing such incidents in goaf areas.
The treatment of advanced hepatocellular carcinoma (HCC) is limited, and immunotherapy is the current research focus of multi-disciplinary collaborative comprehensive treatment of HCC. Herein, we ...constructed a bio-responsive Au-miR-183 inhibitor (Au@miR-183i) delivery system targeting liver cancer stem cells (LCSCs), and adopted the strategy of combining αPD-L1 immunotherapy. The multifunctional Au@miR-183i nanocomplexes (NCs), which self-assemble based on the tumor microenvironment, consume NADPH and H2O2, leading to redox homeostasis disturbance, ROS accumulation, regulation of the LCSC niche, and induction of stemness regression. Moreover, self-assembled Au@miR-183i NCs specifically target the delivery of miR-183i to LCSCs, triggering the immunogenic cell death (ICD) effect, promoting the maturation of dendritic cells, inducing infiltration of CD8+ T cells, and facilitating the transformation of ‘cold’ tumors into ‘hot’ tumors. More importantly, consistent with the results in vitro, Au@miR-183i NCs demonstrated effective tumor targeting and strong ICD induction in vivo, assisted in enhancing αPD-L1 immunotherapy, and activated a robust systemic anti-tumor immune response in tumor-bearing mouse models. Overall, we provide a simple and universal therapeutic strategy by constructing a multifunctional bio-responsive Au@miR-183i NCs delivery system with LCSC targeting capability. Furthermore, nanocomplex-based ICD inducers have great promise in enhancing anti-tumor immunity and the PD-1/PD-L1 blocking efficacy in HCC, which provides a theoretical basis for effectively eliminating LCSCs and achieving a high-efficiency synergistic treatment strategy for HCC.
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•Self-assembled Au@miR-183i NCs target LCSCs for effective delivery of miR-183i.•Au@miR-183i NCs lead to redox homeostasis disturbance inducing stemness regression.•Au@miR-183i NCs exhibit potent ICD-inducing ability.•Au@miR-183i NCs activate anti-tumor immunity and effectively enhances αPD-L1 immunotherapy.
Objective
This study aimed to establish a prognostic stratified model of chemotherapy-based comprehensive treatment for patients with locoregional recurrent nasopharyngeal carcinoma (lrNPC), to help ...individualized treatment decision-making.
Materials and Methods
This study retrospectively reviewed patients with lrNPC who received chemotherapy-based comprehensive treatment from January 1, 2010, to December 31, 2018. A total of 422 eligible patients were divided into test (n = 338) and validation (n = 84) cohorts. A LASSO cox regression model was used to identify significant prognostic factors for overall survival (OS) in the test cohort. A nomogram was then developed based on a combined consideration of clinically meaningful prognostic factors and statistically significant prognostic factors. The performance of the nomogram was assessed with Harrell’s concordance index (C-index) and calibration plots.
Results
Five significant factors were identified: age, albumin (ALB), T stage after recurrent (rT), neutrophil to lymphocyte ratio (NLR), and systematic immune-inflammation index (SII). The nomogram was established with these five factors. C-index was 0.636 in the test cohort and 0.610 in the validation cohort. The calibration curves for the OS rate at 3, and 5 years showed an excellent agreement in both cohorts. In addition, the corresponding risk classification system successfully classified patients into low- and high-risk groups and performed well in stratification (P < 0.001).
Conclusions
The nomogram shows well prognostic performance for lrNPC patients receiving chemotherapy-based comprehensive treatment.
In China, the majority of patients with hepatocellular carcinoma (HCC) result from long-term infection of hepatitis B. Pathologically, HCC is characterized by rich blood supply, multicentric origins, ...early vascular invasion and intrahepatic metastasis. Therefore, HCC is not a local disease but a systemic disease at the beginning of its occurrence. For this reason, a comprehensive treatment strategy should be adopted in the management of HCC, including local treatments (such as surgical resection, radiofrequency ablation, microwave ablation, chemical ablation and cryoablation, etc.), organ-level treatments such as transcatheter arterial infusion of chemotherapy and transcatheter arterial chemoembolization (TACE), and systemic treatments (such as immunotherapy, antiviral therapy and molecular targeted therapy, etc.). This consensus sets forth the minimally-invasive and multidisciplinary comprehensive guideline of HCC, focusing on the following eight aspects (1) using hepaticarteriography, CT hepatic arteriography (CTHA), CT arterial portography (CTAP), lipiodol CT (Lp-CT), TACE-CT to find the intrahepatic lesion and make precise staging (2) TACE combined with ablation or ablation as the first choice of treatment for early stage or small HCC, while other therapies are considered only when ablation is not applicable (3) infiltrating HCC should be regarded as an independent subtype of HCC (4) minimally-invasive comprehensive treatment could be adopted in treating metastatic lymph nodes (5) multi-level subdivision of M-staging should be used for individualized treatment and predicting prognosis (6) HCC with severe hepatic decompensation is the only candidate criterion for liver transplantation (7) bio-immunotherapy, traditional Chinese medicine therapy, antiviral therapy, and psychosocial and psychopharmacological interventions should be advocated through the whole course of HCC treatment (8) implementation of multicenter randomized controlled trials of minimally-invasive therapy versus surgery for early and intermediate stage HCC is recommended.
The incidence of multiple primary carcinomas (MPCs), which are defined as two or more malignancies detected in an individual person, is gradually increasing around the world. According to the timing ...of diagnosis for each constituent tumor, MPCs are classified into 2 categories: synchronous MPCs if constituent tumors emerge simultaneously or within 6 months or metachronous MPCs otherwise. In this report, we describe our recent observation and treatment of a female patient with synchronous primary esophagogastric junction adenocarcinoma, duodenal adenocarcinoma and pancreatic ductal adenocarcinoma (PDAC). To the best of our knowledge, this combination has not yet been reported in the literature. A crucial aspect is the decision regarding which tumor to treat initially and how to schedule further treatments according to individual tumor hazards. Our multidisciplinary team devised an individualized treatment regimen for this patient. The patient ultimately achieved an overall survival time of 18 months, which was much longer than the median survival time (6~11 months) of patients with locally advanced pancreatic cancer. Moreover, treating this rare combination raised a series of diagnostic, etiological and therapeutic questions, motivating us to carry out a critical review of the literature. In summary, an individualized treatment strategy with input from a dedicated multidisciplinary team and consideration of all options at different points along the disease trajectory is essential to optimize outcomes for patients with MPC.
AIM:To explore the treatment methods and curative effect of amblyopia in children, and to analyze the effect of compliance on the treatment process.METHODS:The children with amblyopia treatment since ...January 1st 2010 in General Hospital of Jinan Military Area, were selected and completed follow-up for a total of 129 eyes of 78 patients, including 53 eyes of male in 31 cases and 76 eyes of female in 47 cases, the initial age of 3 to 12 years, the treatment were performed with accurate optometry, reasonable glasses and appropriate to cover the dominant eye based comprehensive therapy and compliance training of the parents and children. The treatment time was 12-36mo, followed up for 3a. The final therapeutic effect was observed and the difference of the stage curative effect between the children with different grade of compliance(good, moderate and poor grade)was compared.RESULTS:In the treatment of 36mo, 106 eyes were cured, 21 eyes were essentially recovered and the total cure rate was 98.4%, which was improved in 2 eyes(1.6%)and was ineffective in 0 eyes(0%); the total effective rate were 100%. The total cure rate was 69% in the treatment of 6mo and there was a significant difference in the cure rate among children with different compliance(overall comparison P<0.001, each comparison P<0.017). In the treatment of 12mo, the total cure rate was 89.1% and the cure rate were significantly different between children with the moderate compliance and the children with good compliance(P<0.05). CONCLUSION:Comprehensive treatment of children with amblyopia can achieve an ideal clinical efficacy. Compliance is an important factor influencing the treatment effect and the treatment process. The parents and children's compliance training can shorten the course of treatment and improve the curative effect.
Traditional Chinese medicine (TCM) has been used successfully to treat rheumatoid arthritis (RA). Qingre Huoxue treatment (Qingre Huoxue decoction (QRHXD)/Qingre Huoxue external preparation (QRHXEP)) ...is a therapeutic scheme of TCM for RA. To date, there have been few studies comparing the efficacy and safety of QRHXD and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of active RA. This was investigated in a multicenter, double-blind, randomized controlled trial involving 468 Chinese patients with active RA disease activity score (DAS)-28 > 3.2 treated with QRHXD/QRHXEP (TCM group), methotrexate plus hydroxychloroquine Western medicine (WM) group, or both integrative medicine (IM) group. Patients were followed up for 24 weeks. The primary outcome measure was the change in DAS-28 from baseline to 24 weeks. The secondary outcome measures were treatment response rate according to American College of Rheumatology 20, 50, and 70% improvement criteria (ACR-20/50/70) and the rate of treatment-related adverse events (TRAEs). The trial was registered at
ClinicalTrials.gov
(NCT02551575). DAS-28 decreased in all three groups after treatment (
p
< 0.0001); the score was lowest in the TCM group (
p
< 0.05), while no difference was observed between the WM and IM groups (
p
> 0.05). At week 24, ACR-20 response was 73.04% with TCM, 80.17% with WM, and 73.95% with IM (based on the full analysis set FAS,
p
> 0.05); ACR-50 responses were 40.87, 47.93, and 51.26%, respectively, (FAS,
p
> 0.05); and ACR-70 responses were 20.87, 22.31, and 25.21%, respectively, (FAS,
p
> 0.05). Thus, treatment efficacy was similar across groups based on ACR criteria. On the other hand, the rate of TRAEs was significantly lower in the TCM group compared to the other groups (
p
< 0.05). Thus, QRHXD/QRHXEP was effective in alleviating the symptoms of active RA—albeit to a lesser degree than csDMARDs—with fewer side effects. Importantly, combination with QRHXD enhanced the efficacy of csDMARDs. These results provide evidence that QRHXD can be used as an adjunct to csDMARDs for the management of RA, especially in patients who experience TRAEs with standard drugs.
Clinical Trial Registration:
ClinicalTrials.gov
, identifier NCTNCT025515.
Congenital hepatoblastoma is an exceedingly rare neoplasm, predominantly documented as isolated instances, with contentious aspects surrounding its therapeutic approaches and prognostic implications. ...This study aims to comprehensively summarize and evaluate the management experience of congenital hepatoblastoma (CHB).
This cohort comprised five infants diagnosed with hepatoblastoma, confirmed through pathological examination, and with an onset of symptoms before 28 days of age. They were enrolled between November 2019 and May 2022. The treatment course they underwent has been summarized, and their prognosis has been subject to analysis.
Distinguishing congenital hepatoblastoma from other medical conditions is typically necessary. Given the patient's tender age, the approach to treatment demands comprehensive assessment, particularly in cases involving unique tumor locations or substantial tumor sizes. The selection of treatment modalities, encompassing preoperative neoadjuvant chemotherapy and surgical techniques, becomes of paramount importance. Furthermore, determining the treatment's endpoint poses a notable challenge and often necessitates a comprehensive evaluation.
For pediatric patients afflicted with CHB, the application of preoperative neoadjuvant chemotherapy mitigates surgical risks, while the incorporation of surgical procedures followed by postoperative chemotherapy significantly enhances the overall prognosis. Additionally, AFP-L3% levels may serve as a valuable adjunctive marker signifying the conclusion of treatment.
•Congenital hepatoblastoma is primarily documented via case reports. with this study reporting a higher number of cases.•Neoadjuvant chemotherapy is safe and effective for patients with CHB when initial surgical removal is not possible.•Three-dimensional imaging, utilizing contrast-enhanced abdominal CT scans, can facilitate tumor resection.•AFP-L3 can serve as a valuable tool for determining the appropriate treatment endpoint.•In certain cases, tumor block resection may lead to an improved prognosis and obviate the need for liver transplantation.
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