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Abstract Penpulimab is an anti-programmed cell death-1 (PD-1) IgG1 antibody with no Fc gamma receptor (FcγR) binding activity, and thus theoretically reduced immune-related adverse events (irAEs) while maintaining efficacy. This single-arm, phase II trial conducted across 20 tertiary care centers in China enrolled adult patients with metastatic nasopharyngeal carcinoma (NPC) who had failed two or more lines of previous systemic chemotherapy. Patients received 200-mg penpulimab intravenously every 2 weeks (4 weeks per cycle) until disease progression or intolerable toxicities. The primary endpoint was objective response rate (ORR) per RECIST (version 1.1), as assessed by an independent radiological review committee. The secondary endpoints included progression-free survival (PFS) and overall survival (OS). One hundred thirty patients were enrolled and 125 were efficacy evaluable. At the data cutoff date (September 28, 2022), 1 patient achieved complete response and 34 patients attained partial response. The ORR was 28.0% (95% CI 20.3–36.7%). The response was durable, with 66.8% still in response at 9 months. Thirty-three patients (26.4%) were still on treatment. The median PFS and OS were 3.6 months (95% CI = 1.9–7.3 months) and 22.8 months (95% CI = 17.1 months to not reached), respectively. Ten (7.6%) patients experienced grade 3 or higher irAEs. Penpulimab has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients, supporting further clinical development as third-line treatment of metastatic NPC.

Glioblastoma (GBM) is known for its aggressive nature and poor prognosis, with currently no effective treatment available. Research has shown that introducing fluorinated functional groups into different parts of natural product quinoline significantly affects its anti-tumor activity. Therefore, this study synthesized the trifluoromethyl quinoline derivative FKL296 to investigate its anti-tumor effect on GBM and reveal its mechanism of action. In vitro and in vivo studies have shown that FKL296 effectively inhibitd the growth of GBM and is relatively safe and low toxicity, whice also induced cell apoptosis and autophagy. Additionally, protein kinase profiling and molecular docking analyses have revealed a strong binding affinity between FKL296 and SGK1. Cellular thermal shift assay experiments have confirmed the targeting of SGK1 by FKL296 and its role in enhancing SGK1 stability. Bioinformatics analysis and pathway validation indicated that FKL296 targeted SGK1 and inhibited autophagy in tumor cells through the mTOR/FOXO3a signaling pathway. In summary, FKL296 may become a promising drug for the treatment of GBM.

The dengue virus, the primary cause of dengue fever, dengue hemorrhagic fever, and dengue shock syndrome, is the most widespread mosquito-borne virus worldwide. In recent decades, the prevalence of dengue fever has increased markedly, presenting substantial public health challenges. Consequently, the development of an efficacious vaccine against dengue remains a critical goal for mitigating its spread. Our research utilized Celcradle™, an innovative tidal bioreactor optimized for high-density cell cultures, to grow Vero cells for dengue virus production. By maintaining optimal pH levels (7.0 to 7.4) and glucose concentrations (1.5 g/L to 3.5 g/L) during the proliferation of cells and viruses, we achieved a peak Vero cell count of approximately 2.46 × 109, nearly ten times the initial count. The use of Celcradle™ substantially decreased the time required for cell yield and virus production compared to conventional Petri dish methods. Moreover, our evaluation of the immunogenicity of the Celcradle™-produced inactivated DENV4 through immunization of mice revealed that sera from these mice demonstrated cross-reactivity with DENV4 cultured in Petri dishes and showed elevated antibody titers compared to those from mice immunized with virus from Petri dishes. These results indicate that the dengue virus cultivated using the Celcradle™ system exhibited enhanced immunogenicity relative to that produced in traditional methods. In conclusion, our study highlights the potential of the Celcradle™ bioreactor for large-scale production of inactivated dengue virus vaccines, offering significant promise for reducing the global impact of dengue virus infections and accelerating the development of effective vaccination strategies.

Abstract Background Induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT) is the standard of care for locoregionally advanced nasopharyngeal carcinoma (LA‐NPC). This intensive treatment regimen increases acute toxicities, which could negatively impact patients' nutritional status. We conducted this prospective, multicentre trial to investigate the effects of IC and CCRT on nutritional status in LA‐NPC patients, so as to provide evidence for further study of nutritional intervention, which was registered in ClinicalTrials.gov (NCT02575547). Methods Patients with biopsy‐proven NPC and planned for IC + CCRT were recruited. IC entailed two cycles of 3‐weekly docetaxel 75 mg/m2 and cisplatin 75 mg/m2; CCRT entailed two to three cycles of 3‐weekly cisplatin 100 mg/m2 depending on the duration of radiotherapy. Nutritional status and quality of life (QoL) were assessed pre‐IC, post‐cycles one and two of IC, W4 and W7 of CCRT. Primary endpoint was the cumulative proportion of ≥ 5.0% weight loss (WL5.0) by the end of treatment (W7‐CCRT). Secondary endpoints included body mass index, NRS2002 and PG‐SGA scores, QoL, hypoalbuminaemia, treatment compliance, acute and late toxicities and survivals. The associations between primary and secondary endpoints were also evaluated. Results One hundred and seventy‐one patients were enrolled. Median follow‐up was 67.4 (IQR: 64.1–71.2) months. 97.7% (167/171) patients completed two cycles of IC, and 87.7% (150/171) completed at least two cycles of concurrent chemotherapy; all, except one patient (0.6%), completed IMRT. WL was minimal during IC (median of 0.0%), but increased sharply at W4‐CCRT (median of 4.0% [IQR: 0.0–7.0%]) and peaked at W7‐CCRT (median of 8.5% [IQR: 4.1–11.7%]). 71.9% (123/171) of patients recorded a WL5.0 by W7‐CCRT, which was associated with a higher malnutrition risk (NRS2002 ≥ 3 points: 87.7% [WL ≥ 5.0%] vs 58.7% [WL

During the transport, storage, and consumption of edible vegetable oils, the color of some freshly refined oils is gradually darkened, which is known as the color reversion. The oil industry has been plagued by the issue for a long time because the dark color of the oil is related to its poor quality and low acceptability for consumers. Color reversion of refined vegetable oils is primarily related to the processing pigments, especially tocored, which is the oxidation product of γ-tocopherol. However, the underlying molecular action mechanism of tocored is not yet fully understood due to the complex transformations of tocored in oil systems. This paper presents a brief description of oil color, followed by an overview of research progress on the mechanism of color reversion. In particular, the effect of minor components (phospholipids and metal ions) on color reversion is highlighted in an attempt to explain the remaining mysteries of color reversion. Furthermore, the measures to restrain color reversion by quality control of the oilseeds, the adjustment of technical parameters of processing, and the storage conditions of refined oils are summarized to provide some references for the oil industry.

In this study, we propose a feature-based method of anatomic plate design for the treatment of individual femoral fractures. This approach improves the design efficiency and convenience of personalized plates. First, we create a parameterized template that represents the typical anatomic features of the femur. This template is produced by reconstructing and parameterizing feature surfaces that are segmented from an average model. Next, the femoral template is deformed under constraints to obtain an individual reference model using several feature parameters of a fractured bone. The major fracture segments are guided automatically to their original anatomic positions. We next design plate templates, namely typical parameterized anatomic plates with specific shapes and structures, and set up the parameter mapping relation between the femoral template and plate template based on the correspondence of feature points. Finally, an initial personalized plate is quickly generated through the instantiation of the selected template with derived parameter values solved from feature mappings. The personalized plate is obtained based on further modification of the initial plate using semantic parameters. Our method supports the automatic restoration of fracture models and achieves the rapid creation of personalized bone plate. The intuitive modification of the shape and structure that arises from our approach contributes to the improvement of design efficiency and quality of personalized plates for individuals.

Personalized anatomic plate is used in the surgical treatment of femoral fracture for the good matching between individual femur and plate. However, the development process of personalized plate is time-consuming and laborious at present due to anatomic and fracture differences between individuals. To improve the efficiency and quality of plate design, this study proposes an integrated computer-aided approach for parametric investigation of anatomic plate design. Based on the constraint deformation of femur template, a reference model was constructed, and major fracture segments were quickly restored to each original anatomic region by rigid registration to the reference model. The experimental results indicate that personalized anatomic plates can be constructed and edited quickly and intuitively with semantic parameters in high level, and contribute to the improvement of design efficiency and quality of customized plates for individuals.

BackgroundNumerous preclinical studies have revealed the complex regulatory mechanisms between anti-angiogenesis and immune inhibition in the tumor immune microenvironment and have proposed the efficacy of combined immunotherapy and anti-angiogenic treatment. Moreover, the combination strategy had been confirmed in a number of clinical trials. In this study, we aimed to evaluate the safety and efficacy of this combination strategy in recurrent/metastatic head and neck squamous cell carcinoma.MethodsIn this real-world study, 43 patients who received the combination of programmed cell death protein 1 (PD-1) inhibitors and anti-vascular endothelial growth factor (VEGF) agents in Zhejiang cancer hospitals between March 2019 and December 2020 were reviewed. Clinical characteristics and follow-up data were collected, and the preliminary efficacy and safety of the combination therapy were assessed.ResultsThe median follow-up time was 12.4 months (range, 3.7-25.3 months), and the follow-up rate was 100%. The median duration of exposure was 9.5 months. Thirty-seven patients (86.0%) reported treatment-related adverse events (TRAEs) of any grade. The most frequently reported events were fatigue, decreased appetite, and hypertension. Grade 3 TRAEs occurred in 8 patients (18.6%), and no grade 4 or 5 TRAEs occurred. Twenty-four patients (55.9%) had an overall response to treatment: 6 (14.0%) had a complete response and 18 (41.9%) had a partial response. In addition, 5 (11.6%) patients had stable disease, and the disease control rate 12 was 67.4%. The median time to response was 1.6 months (range, 1.1-2.8 months). The median progression-free survival (PFS) was not reached, and the 1-year PFS rate was 69.1%. The 1-year overall survival (OS) rate was 87.7%. Patients with primary tumors located in the nasopharynx had better OS than those with tumors outside the nasopharynx. ECOG PS were related to PFS; patients with an ECOG PS of 0 had a slight survival advantage.ConclusionThe combination strategy of anti–PD-1 monoclonal antibodies and anti-VEGF agents was tolerable in patients with recurrent/metastatic head and neck cancer. This treatment exhibited antitumor potential despite the heavily pretreated population.

PurposeWe sought to define the locoregional extension patterns of nasopharyngeal carcinomas (NPCs) by positron emission tomography (PET)/magnetic resonance imaging (MRI) and to improve clinical target volume (CTV) delineation.MethodsBetween May 2017 and March 2021, 331 consecutive patients with nonmetastatic NPCs who underwent pretreatment, simultaneous whole-body PET/MRI for staging were included in this study.ResultsThe high-risk regions included the base of the sphenoid bone, the prestyloid compartment, prevertebral muscle, foramen lacerum, medial pterygoid plate, sphenoidal sinus, clivus, petrous apex, and foramen ovale. When the high-risk regions were invaded, the incidence rates of tumor invasion into the medium-risk regions increased. In contrast, when the high-risk regions were not involved, the incidence rates of tumor invasion into the medium-risk regions were mostly less than 10%, excluding the post-styloid compartment and oropharynx. According to the updated consensus guidelines of the neck node levels for head and neck tumors from 2013, level IIa (77.3%, 256/331), level IIb (75.8%, 251/331), and level VIIa (71.3%, 236/331) were the most frequently involved levels, followed by levels III (42.6%), Va (13.9%), IVa (8.8%), IVb (3.6%), Ib (3.6%), Vb (2.4%), VIIb (2.4%), VIII (1.8%), Vc (0.9%), and Xa (0.3%). Skip lymph node metastasis occurred in only 1.9% of patients.ConclusionsFor NPCs, primary disease and regional lymph node spread follow an orderly pattern, and a skip pattern of lymph node metastasis was unusual. Involved level radiotherapy might be feasible for cervical lymph node levels below the caudal border of cricoid cartilage and level VIIb.

This paper proposes a cooperative learning method for use in physical education, involving two different grouping methods: S-type heterogeneous grouping and “free” grouping. Cooperative learning was found to enhance the effectiveness of basketball skills learning and learning motivation. A comparison was made of the differences between action skills grouping (the control group) and “free” grouping (the experimental group). The ARCS Motivation Scale and Basketball Action Skills Test were used to measure results, and SPSS statistical analysis software was used for relevant statistical processing (with α set to.05). The results showed that overall skills, dribbling and passing among the action skills groups and “free” groupings significantly improved, but results for shooting were not significant; motivation levels for the two grouping methods significantly improved overall, and no significant differences in learning motivation and learning effectiveness were found between the different grouping methods. It is clear that teachers should first establish a good relationship between and with students, and free grouping methods can be used to good effect. Teachers using cooperative learning should intervene in a timely manner and choose suitable grouping methods according to the teaching goals.

To facilitate the construction of intact model of fractured bone and satisfy the representation of fracture information, a novel approach of constructing a restored model of fractured femur (RMFF) based on anatomic feature is put forward. First, the fracture mesh model is divided into major segments by removing the comminuted part. Next, through the constraint-based deformation of parameterized template with a few valid parameters of fracture segments, the intact reference surface model is constructed to represent normal anatomy of individual fractured femur, and the feature points of the reference model are extracted. Then, based on the solution of matrix equations of rigid registration between available feature points of fracture segments and the ones of the reference model, major fracture segments are piecewise adjusted to original proper positions respectively. Finally, the internal part of the reference model cut with the boundary curves of major segments is employed to represent the surface of the comminuted part, and the surface of the comminuted part is merged with adjusted segments to acquire the intact model. Simulation experimental results show that RMFFs can be reconstructed rapidly and accurately according to available information of the fractured femur.

Abstract Background The aim of this study is to evaluate the prognostic value of grading MRI–detected skull-base invasion in nasopharyngeal carcinoma (NPC) with skull-base invasion after intensity-modulated radiotherapy (IMRT). Methods This study is a retrospective chart review of 469 non-metastatic NPC patients with skull-base invasion. Patients were classified as extensive skull-base invasion (ESBI) group and limited skull-base invasion (LSBI) group. Results Multivariate analysis showed that the skull-base invasion (LSBI vs. ESBI) was an independent prognostic predictor of progression free survival (PFS). The estimated 5-year local failure free survival (LFFS), distant metastasis free survival (DMFS), PFS, and overall survival (OS) rates for patients in the T3-LSBI and T3-ESBI group were 92.9% versus 93.5, 89.8% versus 86.1, 81.6% versus 76.4, and 93.5% versus 86.3%, respectively (P > 0.05). Conclusion Grading of MRI-detected skull-base invasion is an independent prognostic factor of NPC with skull-base invasion. It is scientific and reasonable for skull-base invasion as a single entity to be classified as T3 classification.

Background and AimsMalnutrition is a concern in patients with nasopharyngeal carcinoma (NPC) during chemoradiotherapy (CRT)/radiotherapy (RT), which is considered to be related with radiation–induced oral mucositis (ROM). The study aimed to evaluate the nutritional status of NPC patients during RT and investigate its association with ROM.MethodsA prospective study was conducted in NPC patients. Patients were divided into three subgroups (mild, moderate, and severe groups) based on the duration of severe ROM (≥ grade 3). Body weight, body mass index (BMI), albumin, prealbumin, NRS2002, and ROM grade were assessed on a weekly basis before and during CRT/RT. The statistical analysis was performed in the overall group and between three subgroups.ResultsA total of 176 patients were included. In the overall group, body weight and BMI kept decreasing since week 1 of RT, and NRS2002 score and ROM grade increased (p < 0.001). NRS2002 score and prealbumin levels were significantly different between each subgroup (p ≤ 0.046). Significant differences were observed in the proportion of patients receiving enteral nutrition, duration of parenteral nutrition, and total calories provided by nutritional support among three subgroups (p = 0.045–0.001).ConclusionsMalnutrition occurred early in NPC patients and worsened continuously during RT. ROM was strongly associated with nutritional status. Nutritional support should be provided at the start of RT, especially in patients at high-risk of severe ROM.

Purpose: To explore the efficacy of concomitant chemotherapy in intensity-modulated radiotherapy (IMRT) to treat stage II nasopharyngeal carcinoma (NPC).Methods and Materials: In this randomized phase 2 study [registered with ClinicalTrials.gov (NCT01187238)], eligible patients with stage II (2010 UICC/AJCC) NPC were randomly assigned to either IMRT alone (RT group) or IMRT combined with concurrent cisplatin (40 mg/m2, weekly) (CCRT group). The primary endpoint was overall survival (OS). The second endpoints included local failure-free survival (LFFS), regional failure-free survival (RFFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and acute toxicities.Results: Between May 2010 to July 2012, 84 patients who met the criteria were randomized to the RT group (n = 43) or the CCRT group (n = 41). The median follow-up time was 75 months. The OS, LFFS, RFFS, DFS, and DMFS for the RT group and CCRT group were 100% vs. 94.0% (p = 0.25), 93.0% vs. 89.3% (p = 0.79), 97.7% vs. 95.1% (p = 0.54), 90.4% vs. 86.6% (p = 0.72), and 95.2% vs. 94.5% (p = 0.77), respectively. A total of 14 patients experienced disease failure, 7 patients in each group. The incidence of grade 2 to 4 leukopenia was higher in the CCRT group (p = 0.022). No significant differences in liver, renal, skin, or mucosal toxicity was observed between the two groups.Conclusion: For patients with stage II NPC, concomitant chemotherapy with IMRT did not improve survival or disease control but had a detrimental effect on bone marrow function.

HOPX is a transcription factor epigenetically silenced in several cancers. Here the authors, by analysing methylation profiles, identify HOPX as a suppressor of metastasis in nasopharyngeal carcinoma: mechanistically HOPX inhibitsSNAILtranscription through deacetylation-mediated silencing.

Although anatomic plates reflect an important breakthrough in the treatment of distal femur fractures, there are still some patients experiencing healing complications. For individual differences in bone morphology and fractures, the development of patient specific plates is very complex and needs a long cycle. In this study, a parametric approach was proposed to conveniently construct femur models and design their fixation plates. First, the typical femur anatomy was described with the average femur model. Second, five surface features were defined to represent the femur surface model by setting up parameterization and parameter constraints. Third, according to the fracture information of a specific patient, customized plate surface with a suitable contour was created from the reconstructed femur model. Finally, the femur plate was represented by feature parameterization, and the hierarchical constraints between femur parameters and plate parameters were built to construct a plate model. The experimental results showed that the proposed method could effectively represent femur surface shape features and intuitively construct and edit individualized plates with high-level parameters. The method is competitive in time saving and design convenience and may provide a basic tool for digital restoration of incomplete femurs and the design of patient specific femur plates.