Anti-angiogenesis agents plus chemoradiotherapy for locally advanced nasopharyngeal cancer: a systematic review and meta-analysis.

PURPOSE: To evaluate literature evidences about the efficacy and safety of anti-angiogenesis agents plus chemoradiotherapy versus chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma. METHODS: The relevant literature was systematically searched from the date of establishment to April 2023 in PubMed, Embase, Web of Science, The Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biological Medicine, Wanfang and VIP database. Search terms included: Nasopharyngeal Neoplasms, Angiogenesis inhibitors, Endostar, Anlotinib, Apatinib, Bevacizumab, Sunitinib, Pazopanib, Chemoradiotherapy. The literature was strictly screened according to the inclusion and exclusion criteria, and 8 eligible studies were finally included in our meta-analysis (4 randomized controlled trials and 4 retrospective studies). RESULTS: A total of 642 patients were included, with 316 in the anti-angiogenesis agents plus chemoradiotherapy group and 326 in the chemoradiotherapy group. The results of our meta-analysis showed that compared with chemoradiotherapy group, the complete response rate (RR = 1.35, 95% CI 1.05-1.74, P = 0.02), objective response rate (RR = 1.26, 95% CI 1.12-1.43, P = 0.0002) in the anti-angiogenesis agents plus chemoradiotherapy group were significantly improved. In terms of safety, there was a higher incidence of cardiac arrhythmia (RR = 3.63, 95% CI 1.16-11.37, P = 0.03) and hypertension (RR = 1.85, 95% CI 1.04-3.27, P = 0.004) in the anti-angiogenesis agents plus chemoradiotherapy group, while no statistically significant differences were reported in other adverse reactions (all P > 0.05). CONCLUSION: Compared with chemoradiotherapy, anti-angiogenesis agents plus chemoradiotherapy could bring more benefits in terms of short-term efficacy, particularly by notably improving both complete response rate and objective response rate, and overall adverse reactions were acceptable. Anti-angiogenesis agents plus chemoradiotherapy may provide a promising direction for the treatment of locally advanced nasopharyngeal carcinoma. SYSTEMATIC REVIEW REGISTRATION: https://inplasy.com/inplasy-2023-8-0076/ , registration number INPLASY202380076.

Exogenous 24-Epibrassinolide Enhanced Drought Tolerance and Promoted BRASSINOSTEROID-INSENSITIVE2 Expression of Quinoa.

Brassinosteroids (BRs) are involved in the regulation of biotic and abiotic stresses in plants. The molecular mechanisms of BRs that alleviate the drought stress in quinoa have rarely been reported. Here, quinoa seedlings were treated with 24-epibrassinolide (EBR) and we transiently transferred CqBIN2 to the quinoa seedlings' leaves using VIGS technology to analyze the molecular mechanism of the BR mitigation drought stress. The results showed that EBR treatment significantly increased the root growth parameters, the antioxidant enzyme activities, and the osmolyte content, resulting in a decrease in the H2O2, O2∙-, and malondialdehyde content in quinoa. A transcriptome analysis identified 8124, 2761, and 5448 differentially expressed genes (DEGs) among CK and Drought, CK and EBR + Drought, and Drought and EBR + Drought groups. WGCNA divided these DEGs into 19 modules in which these characterized genes collectively contributed significantly to drought stress. In addition, the EBR application also up-regulated the transcript levels of CqBIN2 and proline biosynthesis genes. Silenced CqBIN2 by VIGS could reduce the drought tolerance, survival rate, and proline content in quinoa seedlings. These findings not only revealed that exogenous BRs enhance drought tolerance, but also provided insight into the novel functions of CqBIN2 involved in regulating drought tolerance in plants.

Appropriate Prescribing for older adults with Multimorbidity (Pro-M): protocol for a feasibility study.

BACKGROUND: Potentially inappropriate prescribing is common among older adults with multimorbidity due to various reasons, from concurrent application of multiple single-disease clinical guidelines to fragmentation of care. Interventions such as medication review have been implemented worldwide to reduce inappropriate prescribing for older adults. However, the implementability of such interventions are underexplored in the outpatient clinics in Singapore's public hospitals. Hence, the Pro-M study aims to assess the feasibility of implementing a physician-pharmacist collaborative care intervention in geriatric medicine outpatient clinics to facilitate appropriate prescribing for older adults in Singapore. METHODS: This is a single-arm, non-randomised feasibility study using a pre-post evaluation design. This study consists of two parts: (1) implementation phase of the intervention (6 months) and an (2) evaluation phase (3 months). Eligible patients will be recruited from geriatric medicine outpatient clinics at two public hospitals in Singapore through convenience sampling. The main components of the Pro-M intervention are: (1) pharmacist-facilitated medication reviews with feedback on any medication issues and potential recommendations to physicians, and (2) physicians communicating changes to other relevant prescribers. The evaluation phase will involve surveying and interviewing physicians and pharmacists involved in the implementation of the intervention. A mixed-method approach will be employed for data collection and analysis. The quantitative and qualitative findings will be triangulated and reported using Proctor's implementation outcomes: appropriateness, penetration, acceptability, fidelity, feasibility, and sustainability. A basic cost analysis will be conducted alongside the study. DISCUSSION: This is a phase 2 study to test the feasibility of implementing an intervention that was co-created with stakeholders during phase 1 development of an intervention to optimise prescribing for older adults with multimorbidity. The implementation will be assessed using Proctor's implementation outcomes to provide insights on the process and the feasibility of implementing medication reviews for older adults with multimorbidity as a routine practice in outpatient clinics. Data collected from this study will inform a subsequent scale-up study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05756478. Registered on 06 March 2023.

Matrix metalloproteinase-8 regulates dendritic cell tolerance in late polymicrobial sepsis via the nuclear factor kappa-B p65/ß-catenin pathway.

Background: Tolerogenic dendritic cells (DCs) are associated with poor prognosis of sepsis. Matrix metalloproteinases (MMPs) have been shown to have immunomodulatory effects. However, whether MMPs are involved in the functional reprogramming of DCs is unknown. The study aims to investigate the role of MMPs in sepsis-induced DCs tolerance and the potential mechanisms. Methods: A murine model of late sepsis was induced by cecal ligation and puncture (CLP). The expression levels of members of the MMP family were detected in sepsis-induced tolerogenic DCs by using microarray assessment. The potential roles and mechanisms underlying MMP8 in the differentiation, maturation and functional reprogramming of DCs during late sepsis were assessed both in vitro and in vivo. Results: DCs from late septic mice expressed higher levels of MMP8, MMP9, MMP14, MMP19, MMP25 and MMP27, and MMP8 levels were the highest. MMP8 deficiency significantly alleviated sepsis-induced immune tolerance of DCs both in vivo and in vitro. Adoptive transfer of MMP8 knockdown post-septic bone marrow-derived DCs protected mice against sepsis-associated lethality and organ dysfunction, inhibited regulatory T-cell expansion and enhanced Th1 response. Furthermore, the effect of MMP8 on DC tolerance was found to be associated with the nuclear factor kappa-B p65/ß-catenin pathway. Conclusions: Increased MMP8 levels in septic DCs might serve as a negative feedback loop, thereby suppressing the proinflammatory response and inducing DC tolerance.

Study of Microstructure and Performance Evaluation of Zr-Sn-Nb Joints by Electron Beam Welding.

In this work, Zr-Sn-Nb alloy was joined by electron beam welding (EBW). A defect-free Zr-Sn-Nb joint with sound appearance was obtained. The grains in the weld zone (WZ) and heat-affected zone (HAZ) are significantly coarsened. The columnar grains with a maximum grain size of 0.5 mm are distributed in the upper region of the WZ, while the equiaxed grains are almost located in the bottom region of the WZ. The WZ is mainly composed of the dominant α-Zr, α'-Zr and a few ß phases. The grain orientation of WZ and HAZ is uniform, indicating that no obvious preferred orientation existed. Coarse grains and fine acicular α' phases increase the strength of the joint, but reduce the plasticity and toughness of the joint. The tensile strengths of the joints at room temperature (RT) and 375 °C were 438 MPa and 313 MPa, respectively. The RT impact energy of the joint is 18.5 J, which is only 58.3% of the BM. The high purity of the EBW process and unsignificant grain orientation minimizes damage to the corrosion resistance of Zr-Sn-Nb alloy joints. The corrosion weight gain of the joint specimen and the BM specimen were 12.91 mg/dm2 and 12.64 mg/dm2, respectively, and the thicknesses of the cross-section corrosion layer were 12-15 µm and 9-12 µm, respectively.

Effects of Hydrogenation on the Corrosion Behavior of Zircaloy-4.

Hydrogen plays an important role in the corrosion of zirconium alloys, and the degree of influence highly depends on the alloy composition and conditions. In this work, the effects of hydrogenation on the corrosion behavior of Zircaloy-4 in water containing 3.5 ppm Li + 1000 ppm B at 360 °C/18.6 MPa were investigated. The results revealed that hydrogenation can shorten the corrosion transition time and increase the corrosion rates of Zircaloy-4. The higher corrosion rates can be ascribed to the larger stress in the oxide film of hydrogenated samples, which can accelerate the evolution of the microstructure of the oxide film. In addition, we also found that hydrogenation has little effect on the t-ZrO2 content in the oxide film and there is no direct correspondence between the t-ZrO2 content and the corrosion resistance of the Zircaloy-4.

Research on the Formation Conditions and Preventive Measures of Uranium Precipitates during the Service Process of Medical Isotope Production Reactors.

This study focuses on the Medical Isotope Production Reactor (MIPR), an aqueous homogeneous reactor utilized for synthesizing medical isotopes like 99Mo. A pivotal aspect of MIPR's functionality involves the fuel solution's complex chemical interactions, particularly during reactor operation. These interactions result in the formation of precipitates, notably water filamentous uranium ore and columnar uranium ore, which can impact reactor performance. The research presented here delves into the reactions between liquid fuel uranyl nitrate and key radiolytic products, employing simulation calculations complemented by experimental validation. This approach facilitates the identification of uranium precipitate types and their formation conditions under operational reactor settings. Additionally, the article explores strategies to mitigate the formation of specific uranium precipitates, thereby contributing to the efficient and stable operation of MIPR.

Establishment and Validation of a Survival Benefit Prediction Model for Non-small Cell Lung Cancer after Immunotherapy.

Objective: This study aimed to analyze the prognosis of patients with non-small cell lung cancer (NSCLC) after receiving immunotherapy and construct a prediction model to evaluate the overall survival rate of patients. Methods: This study was a retrospective study that collected data from 493 NSCLC patients who received immunotherapy for the first time. Survival data were analyzed using Cox regression models and the Kaplan-Meier method. The average age of patients was 56 years, and the data collection process included regular outpatient follow-up and observation of overall survival (OS) in the last 36 months. Results: Multivariate analysis identified significant risk factors such as smoking history, age, T stage, and M stage on survival and disease progression. The model's performance indicators (C-index and AUC) and calibration curve verified the model's accuracy and predictive ability. In the training set, the AUCs of 3-year and 5-year survival were 0.761 and 0.763, respectively, and in the validation set, they were 0.739 and 0.761. Conclusion: This study developed a prediction model for evaluating the survival of NSCLC patients after immunotherapy that integrates multiple influencing factors. This predictive model can be used as a tool to assess individual risks in NSCLC patients after immunotherapy, helping clinicians to develop more precise treatment and follow-up plans, potentially improving patient outcomes.

Insight into the Corrosion Inhibition Mechanism of Sodium Silicate on the Magnesium Alloy Surface: Experimental and Theoretical Calculations.

The corrosion inhibition mechanism of sodium silicate (SS) for WE43 magnesium alloy in NaCl solution was investigated by in situ observation, electron probe microanalysis (EPMA), electrochemical test, and theoretical calculations. In situ observation showed that local corrosion was markedly inhibited after the addition of the SS inhibitor. Electrochemical data revealed that a protective layer was formed on the metal/solution interface and an optimum inhibition efficiency of 98.3% in the case of 2.5 g/L SS. A uniform magnesium silicate layer with a thickness of ∼2 µm formed on the uncorroded area was confirmed. Quantum chemical calculations revealed that SiO32- could absorb on the MgO (1 0 0) surface in a parallel orientation through the coordinate bonds between the O and Mg atoms. The distances of Mg-O bonds are 2.052 and 2.249 Å, suggesting that they are coordinated. The adsorption/interaction mechanisms of SiO32- were also analyzed through charge density distribution and atomic densities. Molecular dynamics simulations further confirmed that a uniform SiO32- layer was absorbed on the MgO surface. In the local corroded area, free SiO32- would react with Mg2+ and OH- produced by corrosion to form the insoluble magnesium silicate compound, which hindered the spread of corrosion.

Low-Dose Ketamine-Induced Deficits in Arbitrary Visuomotor Mapping in Monkeys.

Ketamine, an NMDA antagonist, is widely used in clinical settings. Recently, low-dose ketamine has gained attention because of its promising role as a rapid antidepressant. However, the effects of low-dose ketamine on brain function, particularly higher cognitive functions of primate brains, are not fully understood. In this study, we used two macaques as subjects and found that acute low-dose ketamine administration significantly impaired the ability for arbitrary visuomotor mapping (AVM), a form of associative learning (AL) essential for flexible behaviors, including executions of learned stimuli-response contingency or learning of new contingencies. We conducted in-depth analyses and identified intrinsic characteristics of these ketamine-induced functional deficits, including lowered accuracy, prolonged time for planning and movement execution, increased tendency to make errors when visual cues are changed from trial to trial, and stronger impact on combining associative learning and another key higher cognitive function, working memory (WM). Our results shed new light on how associative learning relies on the NMDA-mediated synaptic transmission of the brain and contribute to a better understanding of the potential acute side effects of low-dose ketamine on cognition, which can help facilitate its safe usage in medical practice.

Survival and complications after neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for locally advanced gastric cancer: a systematic review and meta-analysis.

Background: There is increasing evidence that neoadjuvant chemoradiotherapy is superior to neoadjuvant chemotherapy for patients with locally advanced gastric cancer. However, a number of studies have come to the opposite conclusion. Therefore, our meta-analysis is to evaluate the efficacy and safety of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy in the treatment of locally advanced gastric cancer. Methods: We searched Wanfang Database, China National Knowledge Network database, VIP database, China Biomedical Literature Database, PubMed, Embase and Cochrane Library. The searched terms included'Stomach Neoplasms', 'Neoadjuvant Therapy' and 'Chemoradiotherapy'. The retrieval time was from the establishment of the corresponding database to September 2022, and our meta-analysis was performed using RevMan (version 5.3) and Stata (version 17) software. Results: A total of 17 literatures were included, which involved 7 randomized controlled trials and 10 retrospective studies, with a total of 6831 patients. The results of meta-analysis showed that compared with NACT group, the complete response rate(RR=1.95, 95%CI 1.39-2.73, p=0.0001), the partial response rate(RR=1.44, 95%CI 1.22-1.71, p=0.0001), the objective response rate(RR=1.37, 95%CI 1.27-1.54, p=0.00001), the pathologic complete response rate(RR=3.39, 95%CI 2.17-5.30, p=0.00001), the R0 resection rate(RR=1.18, 95%CI 1.09-1.29, p=0.0001) and 3-year overall survival rate(HR=0.89, 95%CI 0.82-0.96, p=0.002) of neoadjuvant chemoradiotherapy group were significantly improved. The results of subgroup analyses of gastric cancer subgroup and gastroesophageal junction cancer subgroup were consistent with the overall results. Meanwhile, the stable disease(RR=0.59, 95%CI:0.44-0.81, P=0.0010) of neoadjuvant chemoradiotherapy group was lower than that of neoadjuvant chemotherapy group, and there were no statistical significance in the progressive disease rate(RR=0.57, 95%CI:0.31-1.03, P=0.06), five-year overall survival rate(HR=1.03, 95%CI:0.99-1.07, P=0.839), postoperative complications and adverse reactions between the neoadjuvant chemoradiotherapy group and neoadjuvant chemotherapy group. Conclusion: Compared with neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy might bring more survival benefits without significantly increasing adverse reactions. neoadjuvant chemoradiotherapy may be a recommended treatment for patients with locally advanced gastric cancer. Systematic Review Registration: https://inplasy.com/inplasy-2022-12-0068/, identifier INPLASY202212068.

Preparation, compatibility and barrier properties of attapulgite/poly (lactic acid)/thermoplastic starch composites.

In this study, AT (attapulgite)/PLA/TPS biocomposites and films were prepared by melt blending technique using PLA and TPS as matrix, polyethylene glycol (PEG) as plasticizing modifier of PLA and AT clay as additive. The effect of AT content on the performance of AT/PLA/TPS composites was investigated. The results showed that, as the AT concentration increased, the fracture surface of the composite showed a bicontinuous phase structure when the AT content was 3 wt%. The rheological properties showed that the addition of AT resulted in more significant deformation of the minor phase, which reduced the phase size and led to lower complex viscosity, and more processability from the industrial perspective. The mechanical properties showed that the addition of AT nanoparticles could simultaneously improve the tensile strength and elongation at break of the composites, reaching a maximum at 3 wt% load. The water vapor barrier performance results showed that AT significantly improved the WVP of the film, and the moisture resistance performance was increased by 254 % compared with the PLA/TPS composite film within 5 h. In conclusion, the obtained AT/PLA/TPS biocomposites showed potential in packaging engineering and injection molding products, especially when renewability and full biodegradability of the material are required.

Dynamic Stimulations with Bioengineered Extracellular Matrix-Mimicking Hydrogels for Mechano Cell Reprogramming and Therapy.

Cells interact with their surrounding environment through a combination of static and dynamic mechanical signals that vary over stimulus types, intensity, space, and time. Compared to static mechanical signals such as stiffness, porosity, and topography, the current understanding on the effects of dynamic mechanical stimulations on cells remains limited, attributing to a lack of access to devices, the complexity of experimental set-up, and data interpretation. Yet, in the pursuit of emerging translational applications (e.g., cell manufacturing for clinical treatment), it is crucial to understand how cells respond to a variety of dynamic forces that are omnipresent in vivo so that they can be exploited to enhance manufacturing and therapeutic outcomes. With a rising appreciation of the extracellular matrix (ECM) as a key regulator of biofunctions, researchers have bioengineered a suite of ECM-mimicking hydrogels, which can be fine-tuned with spatiotemporal mechanical cues to model complex static and dynamic mechanical profiles. This review first discusses how mechanical stimuli may impact different cellular components and the various mechanobiology pathways involved. Then, how hydrogels can be designed to incorporate static and dynamic mechanical parameters to influence cell behaviors are described. The Scopus database is also used to analyze the relative strength in evidence, ranging from strong to weak, based on number of published literatures, associated citations, and treatment significance. Additionally, the impacts of static and dynamic mechanical stimulations on clinically relevant cell types including mesenchymal stem cells, fibroblasts, and immune cells, are evaluated. The aim is to draw attention to the paucity of studies on the effects of dynamic mechanical stimuli on cells, as well as to highlight the potential of using a cocktail of various types and intensities of mechanical stimulations to influence cell fates (similar to the concept of biochemical cocktail to direct cell fate). It is envisioned that this progress report will inspire more exciting translational development of mechanoresponsive hydrogels for biomedical applications.

Dynamic Magneto-Softening of 3D Hydrogel Reverses Malignant Transformation of Cancer Cells and Enhances Drug Efficacy.

High extracellular matrix stiffness is a prominent feature of malignant tumors associated with poor clinical prognosis. To elucidate mechanistic connections between increased matrix stiffness and tumor progression, a variety of hydrogel scaffolds with dynamic changes in stiffness have been developed. These approaches, however, are not biocompatible at high temperature, strong irradiation, and acidic/basic pH, often lack reversibility (can only stiffen and not soften), and do not allow study on the same cell population longitudinally. In this work, we develop a dynamic 3D magnetic hydrogel whose matrix stiffness can be wirelessly and reversibly stiffened and softened multiple times with different rates of change using an external magnet. With this platform, we found that matrix stiffness increased tumor malignancy including denser cell organization, epithelial-to-mesenchymal transition and hypoxia. More interestingly, these malignant transformations could be halted or reversed with matrix softening (i.e., mechanical rescue), to potentiate drug efficacy attributing to reduced solid stress from matrix and downregulation of cell mechano-transductors including YAP1. We propose that our platform can be used to deepen understanding of the impact of matrix softening on cancer biology, an important but rarely studied phenomenon.

Novel use of precipitating hydrophobic injectable liquid (PHIL) in pre-operative angioembolisation of a large posterior auricular arteriovenous malformation.

BACKGROUND: Large arteriovenous malformations are often managed via endovascular embolisation followed by surgical resection. We describe the use of a new liquid embolic agent (LEA) - precipitating hydrophobic injectable liquid (PHIL) and its advantages over existing LEAs. CASE: A 60-year-old male presented with a progressively enlarging right post-auricular arteriovenous malformation. He underwent successive angioembolisation with PHIL and subsequent surgical resection on post-embolisation day 1. CONCLUSION: To our knowledge, this is the first reported case of PHIL being used in pre-operative embolization of a large extra-cranial head and neck AVM. Its excellent penetration into small calibre vessels, decreased glare artefact on imaging and decreased skin pigmentation render it a compelling alternative to existing LEAs.

Actual experience of the training effect of Baduanjin on patients with hemiplegic limb dysfunctions after cerebral infarction: A qualitative study.

AIM: To explore the actual experience of training effect of Baduanjin on patients with hemiplegic limb dysfunctions after cerebral infarction through semistructured interviews and promote Baduanjin training application in clinical and community settings. DESIGN: This qualitative study was conducted using the conventional content analysis approach. METHODS: Twenty-five patients with hemiplegic limb dysfunctions after cerebral infarction were recruited as participants by applying purposive sampling method between September 2017-December 2020 in the physical therapy department of a rehabilitation hospital affiliated with Fujian University of Traditional Chinese Medicine in China. Semistructured interviews were conducted after patients participated in Baduanjin training for 6 weeks. Data were analysed using qualitative content analysis method of Graneheim and Lundman. RESULTS: Three major themes were identified after analysis, namely improving functions of hemiplegic limbs, improving the condition of the entire body and the feelings of practice. The participants indicated that Baduanjin could improve the limb functions and general conditions of hemiplegic patients. Their experience in practicing Baduanjin was generally positive, and they were willing to continue practicing.

Effects of long-term Wuqinxi exercise on working memory in older adults with mild cognitive impairment.

PURPOSE: Although physical exercise may improve memory in older adults, whether the Chinese traditional fitness exercise Wuqinxi improves working memory and delays cognitive deterioration in older adults with mild cognitive impairment (MCI) has not been assessed in randomized controlled experiments. METHODS: Fifty older adults with MCI based on their Montreal Cognitive Assessment scores were randomized to either a Wuqinxi exercise group or a non-exercise control group. The exercise group engaged in Wuqinxi once a week for 60 min each session for 40 weeks. Participants in the control group received no intervention and maintained their regular living habits. The n-back paradigm was used to measure changes in working memory before and after Wuqinxi exercise. RESULTS: In the 0-back task, the response speed of older adults with MCI who participated in Wuqinxi was faster than that of older adults with MCI in the non-exercise control group (P = 0.031); there was no significant difference in accuracy between the two groups (P > 0.05). In the 1-back and 2-back tasks, there was no significant difference in response times or in accuracy between the two groups (P > 0.05). CONCLUSIONS: In this randomized controlled study, participation in long-term Wuqinxi delayed the deterioration of working memory in older adults with MCI, suggesting that this exercise may be an effective intervention to delay or prevent the progression of MCI to Alzheimer's disease.

Nimotuzumab combined with chemoradiotherapy for the treatment of cervical cancer: A meta-analysis of randomized controlled trials.

Objectives: To assess the clinical efficacy and toxicity of nimotuzumab in combination with chemoradiotherapy or chemoradiotherapy alone in the treatment of cervical cancer. Methods: The PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biomedical Medicine, Wanfang, and VIP databases were systematically searched for relevant literature. Ultimately, six randomised controlled trials (n=393) were included in our meta-analysis. Results: A total of 393 patients were included, of which 197 were in the nimotuzumab combined with chemoradiotherapy group and 196 were in the chemoradiotherapy group. The results of our meta-analysis showed that the complete remission rate (risk ratio [RR] = 1.34, 95% confidence interval [CI]: 1.08-1.65, P = 0.007), objective response rate (RR = 1.30, 95% CI: 1.16-1.44, P < 0.05), and three-year survival rate (RR = 1.27, 95% CI: 1.06-1.51, P = 0.008) in the nimotuzumab combined with chemoradiotherapy group were significantly improved compared with the chemoradiotherapy group. This difference was not statistically significant when comparing the incidence of adverse reactions (such as leukocytopenia, gastrointestinal reaction, radiocystitis, and radioproctitis) between the two groups. Conclusions: Nimotuzumab in combination with chemoradiotherapy has some advantages over chemoradiotherapy alone in the treatment of cervical cancer and does not increase toxicity. Therefore, nimotuzumab has the potential to be an effective treatment for cervical cancer; however, further evidence from large-scale randomised controlled trials is needed.

Establishment of a Prognostic Model for Hepatocellular Carcinoma Based on Bioinformatics and the Role of NR6A1 in the Progression of HCC.

Background and Aims: Generally acceptable prognostic models for hepatocellular carcinoma (HCC) are not available. This study aimed to establish a prognostic model for HCC by identifying immune-related differentially expressed genes (IR-DEGs) and to investigate the potential role of NR6A1 in the progression of HCC. Methods: Bioinformatics analysis using The Cancer Genome Atlas and ImmPort databases was used to identify IR-DEGs. Lasso Cox regression and multivariate Cox regression analysis were used to establish a prognostic model of HCC. Kaplan-Meier analysis and the receiver operating characteristic (ROC) curves were used to evaluate the performance of the prognostic model, which was further verified in the International Cancer Genome Consortium (ICGC) database. Gene set enrichment analysis was used to explore the potential pathways of NR6A1. Cell counting kit 8, colony formation, wound healing, and Transwell migration assays using Huh7 cells, and tumor formation models in nude mice were conducted. Results: A prognostic model established based on ten identified IR-DEGs including HSPA4, FABP6, MAPT, NDRG1, APLN, IL17D, LHB, SPP1, GLP1R, and NR6A1, effectively predicted the prognosis of HCC patients, was confirmed by the ROC curves and verified in ICGC database. NR6A1 expression was significantly up-regulated in HCC patients, and NR6A1 was significantly associated with a low survival rate. Gene set enrichment analysis showed the enrichment of cell cycle, mTOR, WNT, and ERBB signaling pathways in patients with high NR6A1 expression. NR6A1 promoted cell proliferation, invasiveness, migration, and malignant tumor formation and growth in vitro and in vivo. Conclusions: An effective prognostic model for HCC, based on a novel signature of 10 immune-related genes, was established. NR6A1 was up-regulated in HCC and was associated with a poor prognosis of HCC. NR6A1 promoted cell proliferation, migration, and growth of HCC, most likely through the cell cycle, mTOR, WNT, and ERBB signaling pathways.

Neoadjuvant chemoradiotherapy for resectable gastric cancer: A meta-analysis.

Objectives: To evaluate the clinical curative effects and toxicity of neoadjuvant chemoradiotherapy for resectable gastric cancer compared to those of neoadjuvant chemotherapy. Methods: A systematic review and meta-analysis of the randomized controlled trials (RCTs) of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy were performed in patients with resectable gastric cancer. Results: Seven RCTs were included (601 patients; 302 in the neoadjuvant chemoradiotherapy group and 299 in the neoadjuvant chemotherapy group). The neoadjuvant chemoradiotherapy group had an increased number of patients with a complete response [odds ratio (OR) = 3.79, 95% confidence interval (CI): 1.68-8.54, p = 0.001] and improved objective response rate (OR = 2.78, 95% CI: 1.69-4.57, p < 0.0001), 1-year (OR = 3.51, 95% CI: 1.40-8.81, p = 0.007) and 3-year (OR = 2.14, 95% CI: 1.30-3.50, p = 0.003) survival rates, R0 resection rate (OR = 2.21, 95% CI: 1.39-3.50, p = 0.0008), and complete pathologic response (OR = 4.39, 95% CI: 1.59-12.14, p = 0.004). Regarding the incidence of adverse effects after neoadjuvant therapy, only the occurrence rate of gastrointestinal reaction in the neoadjuvant chemoradiotherapy group was higher than that in the neoadjuvant chemotherapy group (OR = 1.76, 95% CI: 1.09-2.85, p = 0.02), and there was no significant difference in other adverse effects. There was no difference in the incidence of postoperative complications between the two groups. Conclusion: Neoadjuvant chemoradiotherapy for resectable gastric cancer has several advantages in terms of efficacy and safety compared to neoadjuvant chemotherapy. Therefore, neoadjuvant chemoradiotherapy has great potential as an effective therapy for resectable gastric cancers. Systematic Review Registration: https://inplasy.com/inplasy-2022-3-0164, registration number INPLASY202230164.