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PURPOSE: This prospective study aimed to assess the predictive value of mono-exponential and multiple mathematical diffusion-weighted imaging (DWI) models in determining the response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). METHODS: The study included 103 LARC patients scheduled for preoperative chemoradiotherapy between December 2021 and June 2023 Magnetic resonance imaging (MRI) scans were performed using a 3.0-T MR scanner, encompassing sagittal, axial, and oblique coronal T2-weighted images without fat saturation, along with DWI perpendicular to the rectum's long axis. Various DWI parameters, including apparent diffusion coefficient (ADC), stretched exponential model (SEM), continuous-time random-walk model (CTRW), and fractional-order calculus model (FROC), were measured. The pathologic complete response (pCR) rate and tumor downstaging (T-downstage) rate were determined. RESULTS: After nCRT, SEM-α, SEM-DDC, CTRW-α, CTRW-ß, CTRW-D, FROC-ß, and ADC values were significantly higher in the pCR group compared to the non-pCR group (all P < 0.05). SEM-DDC, CTRW-α, CTRW-D, FROC-ß, FROC-µ, and ADC values were significantly higher in the T-downstage group (ypT0-1) than in the non-T-downstage group (ypT2-4) (P < 0.05). The combination of CTRW (α + ß + D) exhibited the best diagnostic performance for assessing pCR after nCRT (AUC = 0.840, P < 0.001). Pre-nCRT CTRW (α + ß) demonstrated a predictive AUC of 0.652 (95%CI: 0.552-0.743), 90.3% sensitivity, and 43.1% specificity for pCR. Regarding T-downstage assessment after nCRT, the combination of CTRW (α + D) yielded the best diagnostic performance (AUC = 0.877, P = 0.048). CONCLUSION: In LARC patients, imaging markers derived from CTRW show promise in predicting tumor response before nCRT and assessing pCR after nCRT.

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BACKGROUND: Gastric cancer (GC) stands out as one of the most prevalent malignancies affecting the digestive system, characterized by a substantial incidence rate and mortality. Maternal embryonic leucine zipper kinase (MELK) has been implicated in the advancement of various cancer types and the modulation of the tumor microenvironment. This study aims to delve into the involvement of MELK in chemoresistance and the tumor microenvironment of GC. METHODS: The MELK expression was detected using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry. Lentiviral transfection was employed to establish stable cell lines with either overexpressed or silenced MELK. The impact of MELK on the chemoresistance of GC cells and the polarization of macrophages was investigated through in vitro and in vivo functional assays. Additionally, the correlation between MELK and the cytokines colony-stimulating factor 1 (CSF-1), as well as stromal macrophages, was analysed. The prognostic significance of MELK, CSF-1, and CD206 expression levels in clinical samples was further investigated. RESULTS: MELK was found to be highly expressed in chemoresistant GC cells and tissues. Furthermore, both in vitro and in vivo assays indicated that MELK overexpression conferred chemoresistance in GC cells. Additionally, MELK overexpression was observed to induce M2 macrophage polarization via the CSF-1/JAK2/STAT3 pathway, thereby contributing to chemoresistance within the tumor microenvironment. The expression of MELK in GC tissues from neoadjuvant chemotherapy patients correlated positively with CSF-1 and CD206. Moreover, patients with higher expression levels of MELK, CSF-1, or CD206 exhibited significantly shorter OS and DFS rates. CONCLUSIONS: Our investigation underscores the critical role of MELK in promoting chemoresistance and inducing M2 macrophage polarization in GC. It proposes novel targets and methods for the treatment of GC, as well as prognostic factors for neoadjuvant chemotherapy.

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PURPOSE: This study aims to explore the relationship between apparent diffusion coefficient (ADC) and fractional-order calculus (FROC)-specific parameters with prognostic indicators and Kirsten rat sarcoma viral oncogene homologue (KRAS) mutation status in rectal cancer. METHODS: One hundred fifty-eight patients with rectal cancer were retrospectively enrolled. Histogram measurements of ADC, diffusion coefficient (D), intravoxel diffusion heterogeneity (ß), and a microstructural quantity (µ) were estimated for the whole-tumor volume. The relationships between histogram measurements and prognostic indicators were evaluated. The efficacy of histogram measurements, both conducted singly and in conjunction, for evaluating different KRAS mutation statuses was also assessed. The performance of mean and median histogram measurements in evaluating various KRAS mutation statuses was assessed using Receiver Operating Characteristic (ROC) curve analysis. A p-value of less than 0.05 was considered statistically significant. RESULTS: The histogram measurements of ADC, D, ß, and µ differed significantly between well-moderately differentiated groups and poorly differentiated groups, T1-2 and T3-4 subgroups, lymph node metastasis (LNM)-negative and LNM-positive subgroups, extranodal extension (ENE)-negative and ENE-positive subgroups, tumor deposit (TD)-negative and TD-positive subgroups, and lymphovascular invasion (LVI)-negative and LVI-positive subgroups. The combination of Dmean, ßmean, and µmean achieved the highest performance [The area under the ROC curve (AUC) = 0.904] in evaluating the KRAS mutation status. CONCLUSION: When assessing parameters from the FROC model as potential biomarkers through histograms, they surpass traditional ADC values in distinguishing prognostic indicators and determining KRAS mutation status in rectal cancer.

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OBJECTIVES: To explore diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) for assessing pathological prognostic factors in patients with rectal cancer. MATERIALS AND METHODS: A total of 162 patients (105 males; mean age of 61.8 ± 13.1 years old) scheduled to undergo radical surgery were enrolled in this prospective study. The pathological prognostic factors included histological differentiation, lymph node metastasis (LNM), and extramural vascular invasion (EMVI). The DWI, IVIM, and DKI parameters were obtained and correlated with prognostic factors using univariable and multivariable logistic regression. Their assessment value was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Multivariable logistic regression analyses showed that higher mean kurtosis (MK) (odds ratio (OR) = 194.931, p < 0.001) and lower apparent diffusion coefficient (ADC) (OR = 0.077, p = 0.025) were independently associated with poorer differentiation tumors. Higher perfusion fraction (f) (OR = 575.707, p = 0.023) and higher MK (OR = 173.559, p < 0.001) were independently associated with LNMs. Higher f (OR = 1036.116, p = 0.024), higher MK (OR = 253.629, p < 0.001), lower mean diffusivity (MD) (OR = 0.125, p = 0.038), and lower ADC (OR = 0.094, p = 0.022) were independently associated with EMVI. The area under the ROC curve (AUC) of MK for histological differentiation was significantly higher than ADC (0.771 vs. 0.638, p = 0.035). The AUC of MK for LNM positivity was higher than f (0.770 vs. 0.656, p = 0.048). The AUC of MK combined with MD (0.790) was the highest among f (0.663), MK (0.779), MD (0.617), and ADC (0.610) in assessing EMVI. CONCLUSION: The DKI parameters may be used as imaging biomarkers to assess pathological prognostic factors of rectal cancer before surgery. CLINICAL RELEVANCE STATEMENT: Diffusion kurtosis imaging (DKI) parameters, particularly mean kurtosis (MK), are promising biomarkers for assessing histological differentiation, lymph node metastasis, and extramural vascular invasion of rectal cancer. These findings suggest DKI's potential in the preoperative assessment of rectal cancer. KEY POINTS: Mean kurtosis outperformed the apparent diffusion coefficient in assessing histological differentiation in resectable rectal cancer. Perfusion fraction and mean kurtosis are independent indicators for assessing lymph node metastasis in rectal cancer. Mean kurtosis and mean diffusivity demonstrated superior accuracy in assessing extramural vascular invasion.

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Introduction: Stress dynamic computed tomography myocardial perfusion imaging (CT-MPI) is an accurate quantitative method for diagnosing myocardial ischemia in coronary artery disease (CAD). However, its clinical application has been limited, partly due to the varied cutoff values for absolute myocardial blood flow (MBFa) and the uncertain value of the relative myocardial blood flow ratio (MBF-ratio). This study aimed to compare the diagnostic efficacy of and investigate the optimal cutoff values for MBFa and the MBF-ratio in CT-MPI for diagnosing myocardial ischemia in patients with hemodynamically significant CAD. Methods: Patients with suspected or known hemodynamically significant CAD who underwent CT-MPI + CT angiography and invasive coronary angiography (ICA)/fractional flow reserve (FFR) between October 2020 and December 2023 were retrospectively evaluated. ICA ≥80% or FFR ≤0.8 were set as the diagnostic standards for functional ischemia. The patients and vessels were categorized into ischemic and non-ischemic groups, and differences in MBFa and the MBF-ratio were compared between the groups. The area under the curve (AUC) and optimal cutoff values were calculated. Diagnostic efficacy parameters, such as sensitivity, specificity, and accuracy, were also compared. In addition, a consistency test was performed. Results: A total of 46 patients (mean age: 65.37 ± 8.25 years; 120 vessels) were evaluated. Hemodynamically significant stenosis was detected in 30/46 patients (48%) and 81/120 vessels (67.5%). The MBFa and MBF-ratio values were significantly lower in the ischemic than in the non-ischemic group; in the per-vessel analysis, the MBFa values were 73 vs. 128 (P < 0.001) and the MBF-ratio values were 0.781 vs. 0.856 (P < 0.001), respectively. The optimal cutoff values for MBFa and the MBF-ratio were 117.71 and 0.67, respectively. MBFa demonstrated a sensitivity, specificity, accuracy, AUC, positive predictive value, negative predictive value, and kappa value of 97.44%, 74.07%, 81.66%, 0.936 [95% confidence interval (CI): 0.876-0.973, P < 0.001], 63.33%, 98.36%, and 0.631 (95% CI: 0.500-0.762), respectively. The corresponding values for the MBF-ratio were 92.31%, 85.19%, 87.5%, 0.962 (95% CI: 0.911-0.989, P < 0.001), 75%, 95.83%, and 0.731 (95% CI: 0.606-0.857, P < 0.001), with no significant difference (P = 0.1225). Conclusion: Both MBFa and the MBF-ratio exhibit excellent diagnostic performance for myocardial ischemia in patients with hemodynamically significant CAD. The MBF-ratio is more robust than MBFa for interpreting CT-MPI findings in clinical practice, which is useful for radiologists and clinicians implementing CT-MPI.

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PURPOSE: To evaluate the diagnostic performance of Golden-Angle Radial Sparse Parallel (GRASP) MRI in identifying pathological stage T0-1 (ypT0-1) after neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer, compared to T2-weighted imaging (T2WI) combined with Diffusion Weighted Imaging (DWI). METHODS: In this retrospective study, 168 patients were carefully selected based on inclusion criteria that targeted individuals with biopsy-confirmed primary rectal adenocarcinoma, identified via MRI as having locally advanced disease (≥ T3 and/or positive lymph node results) prior to nCRT. Post-nCRT, all MRI images obtained after nCRT were assessed by two observers independently. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for identifying ypT0-1 based on GRASP and T2 + DWI were calculated. Multivariable regression analysis was used to explore the factors independently associated with ypT0-1 tumor. RESULTS: 45 patients out of these cases were ypT0-1, and the accuracy, sensitivity, specificity, PPV, and NPV of GRASP were higher than the T2 + DWI (88% vs 74%, 93% vs 71%, 86% vs 75%, 71% vs 52% and 97% vs 88%), the AUC in identifying ypT0-1 tumor based on GRASP was 0.90 (95% CI:0.84, 0.94), which was better than the T2 + DWI (0.73; 95% CI: 0.66, 0.80). Multivariable logistic regression analysis showed that the yT stage on GRASP scans was the only factor independently associated with ypT0-1 tumor (P < 0.001). CONCLUSION: The GRASP helped distinguish ypT0-1 tumor after nCRT and can select patients who may be suitable for local excision.

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Objective: This study aimed to analyze the relationship between the sleep quality of healthcare professionals and the incidence of overweight and obesity, exploring the potential impact of sleep quality on the onset of overweight and obesity in order to provide a scientific basis for formulating effective health intervention measures. Methods: A convenience sampling method was used to conduct a survey on the sleep characteristics and obesity status among healthcare professionals at Peking Union Medical College Hospital and Tianjin Dongli District Traditional Chinese Medicine Hospital. The survey was conducted via online questionnaires, which included demographic data, the Pittsburgh Sleep Quality Index (PSQI), height, weight, and related sleep, exercise, and dietary habits. Univariate and multivariate logistic regression analyses were applied to study the relationship between sleep quality and overweight/obesity among healthcare professionals. Results: A total of 402 questionnaires were distributed, with a 100% retrieval rate, yielding 402 valid questionnaires. The average body mass index of the 402 participants was 23.22 ± 3.87 kg/m^2. Among them, 144 cases were overweight or obese, accounting for 35.8% (144/402) of the total. The prevalence of poor sleep quality among healthcare professionals was 27.4% (110/402), with an average PSQI score of 8.37 ± 3.624. The rate of poor sleep quality was significantly higher in the overweight and obese group compared to the normal weight group (36.1% vs. 22.5%, p = 0.003). The multivariate analysis indicated that gender, marital status, lower education level, sleep duration (odds ratio [OR] =1.411, 95% confidence interval [CI] 1.043-1.910, p = 0.026), and sleep disturbances (OR = 1.574, 95%CI 1.123-2.206, p = 0.008) were significant risk factors for overweight and obesity among healthcare professionals. Conclusion: Overweight or obese healthcare professionals had poorer sleep quality compared to those with a normal weight. Sleep duration and sleep disorders were identified as independent risk factors for overweight or obesity in healthcare professionals. Increasing sleep duration and improving sleep disorders may play a positive role in controlling overweight and obesity among healthcare professionals.

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PURPOSE: This study explored models of monoexponential diffusion-weighted imaging (DWI), diffusion kurtosis imaging (DKI), stretched exponential (SEM), fractional-order calculus (FROC), and continuous-time random-walk (CTRW) as diagnostic tools for assessing pathological prognostic factors in patients with resectable rectal cancer (RRC). METHODS: RRC patients who underwent radical surgery were included. The apparent diffusion coefficient (ADC), the mean kurtosis (MK) and mean diffusion (MD) from the DKI model, the distributed diffusion coefficient (DDC) and α from the SEM model, D, ß and u from the FROC model, and D, α and ß from the CTRW model were assessed. RESULTS: There were a total of 181 patients. The area under the receiver operating characteristic (ROC) curve (AUC) of CTRW-α for predicting histology type was significantly higher than that of FROC-u (0.780 vs. 0.671, p = 0.043). The AUC of CTRW-α for predicting pT stage was significantly higher than that of FROC-u and ADC (0.786 vs.0.683, p = 0.043; 0.786 vs. 0.682, p = 0.030), the difference in predictive efficacy of FROC-u between ADC and MK was not statistically significant [0.683 vs. 0.682, p = 0.981; 0.683 vs. 0.703, p = 0.720]; the difference between the predictive efficacy of MK and ADC was not statistically significant (p = 0.696). The AUC of CTRW (α + ß) (0.781) was significantly higher than that of FROC-u (0.781 vs. 0.625, p = 0.003) in predicting pN stage but not significantly different from that of MK (p = 0.108). CONCLUSION: The CTRW and DKI models may serve as imaging biomarkers to predict pathological prognostic factors in RRC patients before surgery.

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Virtual agglomeration of manufacturing has become a new driving force for improving the green total factor productivity of enterprises, which is of great significance in achieving the sustainable development of manufacturing enterprises and the construction of manufacturing power. This paper clarifies the connotation, model, and characteristics of manufacturing virtual agglomeration. Based on the five dimensions of virtual agglomeration platform, digitization of subjects, data center, virtual cooperation network, and logistics service, this paper constructs an index system for the manufacturing virtual agglomeration. Entropy weight method was used to measure the level of manufacturing virtual agglomeration from 2012 to 2021. Furthermore, this paper analyzes and tests the influence mechanism of manufacturing virtual agglomeration on the green total factor productivity of enterprises. This paper finds that manufacturing virtual agglomeration improves the green total factor productivity of enterprises, which shows a nonlinear relationship. The mechanism test results show that manufacturing virtual agglomeration improves the green total factor productivity of enterprises by accelerating green technology innovation, forming a scale economy, and reducing transaction costs. The heterogeneity analysis shows that the promotion effect of virtual agglomeration in manufacturing on the green total factor productivity of enterprises is affected by the property rights and scale of the enterprise.

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Neurorestoratology constitutes a novel discipline aimed at the restoration of damaged neural structures and impaired neurological functions. This area of knowledge integrates and compiles all concepts and strategies dealing with the neurorestoration. Although currently, this discipline has already been well recognized by physicians and scientists throughout the world, this article aimed at broadening its knowledge to the academic circle and the public society. Here we shortly introduced why and how Neurorestoratology was born since the fact that the central nervous system (CNS) can be repaired and the subsequent scientific evidence of the neurorestorative mechanisms behind, such as neurostimulation or neuromodulation, neuroprotection, neuroplasticity, neurogenesis, neuroregeneration or axonal regeneration or sprouting, neuroreplacement, loop reconstruction, remyelination, immunoregulation, angiogenesis or revascularization, and others. The scope of this discipline is the improvement of therapeutic approaches for neurological diseases and the development of neurorestorative strategies through the comprehensive efforts of experts in the different areas and all articulated by the associations of Neurorestoratology and its journals. Strikingly, this article additionally explores the "state of art" of the Neurorestoratology field. This includes the development process of the discipline, the achievements and advances of novel neurorestorative treatments, the most efficient procedures exploring and evaluating outcome after the application of pioneer therapies, all the joining of a multidisciplinary expert associations and the specialized journals being more and more impact. We believe that in a near future, this discipline will evolve fast, leading to a general application of cell-based comprehensive neurorestorative treatments to fulfill functional recovery demands for patients with neurological deficits or dysfunctions.

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Neurorestorative cell therapies have been tested to treat patients with nervous system diseases for over 20 years. Now it is still hard to answer which kinds of cells can really play a role on improving these patients' quality of life. Non-randomized clinical trials or studies could not provide strong evidences in answering this critical question. In this review, we summarized randomized clinical trials of cell therapies for central nervous diseases, such as stroke, spinal cord injury, cerebral palsy (CP), Parkinson's disease (PD), multiple sclerosis (MS), brain trauma, amyotrophic lateral sclerosis (ALS), etc. Most kinds of cell therapies demonstrated negative results for stoke, brain trauma and amyotrophic lateral sclerosis. A few kinds of cell therapies showed neurorestorative effects in this level of evidence-based medicine, such as olfactory ensheating cells for chronic ischemic stroke. Some kinds of cells showed positive or negative effects from different teams in the same or different diseases. We analyzed the possible failed reasons of negative results and the cellular bio-propriety basis of positive results. Based on therapeutic results of randomized control trials and reasonable analysis, we recommend: (1) to further conduct trials for successful cell therapies with positive results to increase neurorestorative effects; (2) to avoid in repeating failed cell therapies with negative results in same diseases because it is nonsense for them to be done with similar treatment methods, such as cell dosage, transplanting way, time of window, etc. Furthermore, we strongly suggest not to do non-randomized clinical trials for cells that had shown negative results in randomized clinical trials.

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Delivering drugs to the brain has always been a challenging task due to the restrictive properties of the blood-brain barrier (BBB). Intranasal delivery is therefore emerging as an efficient method of administration, making it easy to self-administration and thus provides a non-invasive and painless alternative to oral and parenteral administration for delivering therapeutics to the central nervous system (CNS). Recently, drug formulations have been developed to further enhance this nose-to-brain transport, primarily using nanoparticles (NPs). Therefore, the purposes of this review are to highlight and describe the anatomical basis of nasal-brain pathway and provide an overview of drug formulations and current drugs for intranasal administration in CNS disease.

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Stress is one of the most serious consequences of life leading to several chronic diseases and neurodegeneration. Recent studies show that emotional stress and other kinds of anxiety and depression adversely affects Parkinson's disease symptoms. However, the details of how stress affects Parkinson's disease is still not well known. Traumatic brain injury, stroke, diabetes, post-traumatic stress disorders are well known to modify the disease precipitation, progression and persistence. However, show stress could influence Parkinson's disease is still not well known. The present investigation we examine the role of immobilization stress influencing Parkinson's disease brain pathology in model experiments. In ore previous report we found that mild traumatic brain injury exacerbate Parkinson's disease brain pathology and nanodelivery of dl-3-n-butylphthalide either alone or together with mesenchymal stem cells significantly attenuated Parkinson's disease brain pathology. In this chapter we discuss the role of stress in exacerbating Parkinson's disease pathology and nanowired delivery of dl-3-n-butylphthalide together with monoclonal antibodies to alpha synuclein (ASNC) is able to induce significant neuroprotection. The possible mechanisms of dl-3-n-butylphthalide and ASNC induced neuroprotection and suitable clinical therapeutic strategy is discussed.

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dl-3-n-Butylphthalide is a potent synthetic Chinese celery extract that is highly efficient in inducing neuroprotection in concussive head injury (CHI), Parkinson's disease, Alzheimer's disease, stroke as well as depression, dementia, anxiety and other neurological diseases. Thus, there are reasons to believe that dl-3-n-butylphthalide could effectively prevent Alzheimer's disease brain pathology. Military personnel during combat operation or veterans are often the victims of brain injury that is a major risk factor for developing Alzheimer's disease in their later lives. In our laboratory we have shown that CHI exacerbates Alzheimer's disease brain pathology and reduces the amyloid beta peptide (AßP) inactivating enzyme neprilysin. We have used TiO2 nanowired-dl-3-n-butylphthalide in attenuating Parkinson's disease brain pathology exacerbated by CHI. Nanodelivery of dl-3-n-butylphthalide appears to be more potent as compared to the conventional delivery of the compound. Thus, it would be interesting to examine the effects of nanowired dl-3-n-butylphthalide together with nanowired delivery of neprilysin in Alzheimer's disease model on brain pathology. In this investigation we found that nanowired delivery of dl-3-n-butylphthalide together with nanowired neprilysin significantly attenuated brain pathology in Alzheimer's disease model with CHI, not reported earlier. The possible mechanism and clinical significance is discussed based on the current literature.

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Military personnel are often victims of spinal cord injury resulting in lifetime disability and decrease in quality of life. However, no suitable therapeutic measures are still available to restore functional disability or arresting the pathophysiological progression of disease in victims for leading a better quality of life. Thus, further research in spinal cord injury using novel strategies or combination of available neuroprotective drugs is urgently needed for superior neuroprotection. In this regard, our laboratory is engaged in developing TiO2 nanowired delivery of drugs, antibodies and enzymes in combination to attenuate spinal cord injury induced pathophysiology and functional disability in experimental rodent model. Previous observations show that histamine antagonists or antioxidant compounds when given alone in spinal cord injury are able to induce neuroprotection for short periods after trauma. In this investigation we used a combination of histaminergic drugs with antioxidant compound H-290/51 using their nanowired delivery for neuroprotection in spinal cord injury of longer duration. Our observations show that a combination of H3 receptor inverse agonist BF-2549 with H3 receptor antagonist and H4 receptor agonist clobenpropit induced neuroprotection is potentiated by antioxidant compound H-290/51 in spinal cord injury. These observations suggests that histamine receptors are involved in the pathophysiology of spinal cord injury and induce superior neuroprotection in combination with an inhibitor of lipid peroxidation H-290/51, not reported earlier. The possible mechanisms and significance of our findings in relation to future clinical approaches in spinal cord injury is discussed.

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BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly used in locally advanced gastric cancer (LAGC), but the clinical safety and efficacy are still controversial. This study aims to compare perioperative chemotherapy (PEC) with adjuvant chemotherapy (AC) for resectable LAGC. METHODS: Patients who underwent D2 gastrectomy for resectable LAGC were retrospectively reviewed, and divided into NSA group (NAC plus surgery and AC) and SA group (surgery followed by AC). The baseline characteristics and perioperative data were compared. Survival analysis was based on Kaplan-Meier method. Multivariate analyses for prognostic factors were based on the Cox regression. RESULTS: A total of 450 patients were eligible for this study. 218 patients received NAC plus surgery and AC, while 232 upfront surgery followed by AC. The baseline characteristics were comparable between the two groups. NSA group showed significant superiority in R0 resection rate (P = 0.014), excised tumor size (P = 0.038), and tumor downstage (all P < 0.001). NAC did not affect postoperative complications or AC-related grade 3/4 adverse events. Patients in NSA group achieved significantly longer OS (P = 0.021) and DFS (P = 0.002). The Cox regression model showed that NAC was independently associated with better OS (HR 0.245, P = 0.039) and DFS (HR 0.591, P = 0.031). CONCLUSIONS: Compared with SA, the administration of NSA was considered safe and feasible for achieving higher R0 resection rate without increasing the postoperative complications or AC-related grade 3/4 adverse events, and NAC was independently associated with better OS and DFS for resectable LAGC.

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Inclusive green growth (IGG) has become a worldwide consensus to achieve the target of sustainable development goals. Although the prominent role of digital finance (DF) against the pandemic has drawn considerable attention from policymakers, its plausible effect on IGG and underlying mechanisms have not been distinctly explored in academia. The aim of the study is to explore the causal effect of DF on IGG based on prefecture city-level data from 2011 to 2019 in China. To this end, we employed the non-radial direction distance function approach within the global production technology to evaluate the aggregate IGG performance and its three sub-dimensions. The empirical results demonstrate that DF exerts a significant promotional effect on urban IGG. This finding continues to survive in an extensive set of robustness checks using an alternative dependent variable, model specifications, instrumental variable, and difference-in-difference approaches to address the endogeneity concerns. Meanwhile, sub-dimensional regressions show that this positive effect is driven predominantly by the scale economy of DF, while the depth of usage and digitalization playing a minor role. Moreover, we uncover that DF enhances IGG by leveraging greater marginal product of labor rather than capital, improving environmental externalities, increasing fuller employment, and reducing rural-urban income inequality. However, we also reveal the dark side of DF on imbalanced regional development. The promotional effect of DF on IGG is only prominent for cities with better inherent comparative advantages, and we are thus likely to see a widening digital divide resulting from the "Matthew effect" on regional disparity without timely policy interventions.

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Background: The objective of this retrospective investigation is to evaluate the diagnostic efficacy of a dual-parameter strategy that integrates either time-resolved angiography with stochastic trajectories (TWIST) or golden-angle radial sparse parallel (GRASP)-derived dynamic contrast agent-enhanced magnetic resonance imaging (DCE-MRI) with diffusion-weighted imaging (DWI) for the identification of poorly differentiated rectal cancer (RC). The purpose of this investigation is to contrast the aforementioned methodology with conventional single-factor assessments that rely solely on DWI, and ascertain its comparative efficacy. Methods: This study was not registered on a clinical trial platform. Consecutive individuals diagnosed with non-mucinous rectal adenocarcinoma through endoscopy-guided biopsy between December 2020 and October 2022 were involved in our study. These patients had also undergone DCE-MRI and DWI. The perfusion metrics of influx forward volume transfer constant (Ktrans) and rate constant (Kep), along with the apparent diffusion coefficient (ADC), were quantified by a pair of investigators. The study compared the area under the curve (AUC) of the receiver operating characteristic (ROC) for both sequences to identify poorly differentiated RC. The investigation incorporated patients who fulfilled the specified criteria. The inclusion criteria for the investigation were as follows: (I) a diagnosis of RC proved through pathological examination, either via endoscopically-guided biopsy or surgical resection; (II) availability of complete MRI images; (III) absence of any prior history of neoadjuvant chemoradiotherapy during the MRI scan. Results: Our investigation comprised a total of 179 participants. Compared to diffusion parameter alone, an integrated assessment of diffusion parameter (ADC) and perfusion parameters (Ktrans or Kep) obtained with GRASP leads to a superior diagnostic accuracy (AUC, 0.97±0.02 vs. 0.89±0.03, 0.97±0.02 vs. 0.89±0.03, P=0.005 and 0.003, respectively); however, there was no additional benefit from ADC with perfusion parameters obtained from TWIST (Ktrans or Kep) (AUC, 0.93±0.04 vs. 0.89±0.03, 0.93±0.03 vs. 0.89±0.03; P= 0.955 and 0.981, respectively, for the integration of ADC with Ktrans and Kep). Conclusions: By integrating diffusion and perfusion features into a dual-parameter model, the GRASP method enhances the diagnostic efficacy of MRI in discriminating RCs with poor differentiation. Conversely, the TWIST approach did not yield the aforementioned outcome.

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Parkinson's disease (PD) in military personnel engaged in combat operations is likely to develop in their later lives. In order to enhance the quality of lives of PD patients, exploration of novel therapy based on new research strategies is highly warranted. The hallmarks of PD include increased alpha synuclein (ASNC) and phosphorylated tau (p-tau) in the cerebrospinal fluid (CSF) leading to brain pathology. In addition, there are evidences showing increased histaminergic nerve fibers in substantia niagra pars compacta (SNpc), striatum (STr), and caudate putamen (CP) associated with upregulation of histamine H3 receptors and downregulation of H4 receptors in human brain. Previous studies from our group showed that modulation of potent histaminergic H3 receptor inverse agonist BF-2549 or clobenpropit (CLBPT) partial histamine H4 agonist with H3 receptor antagonist induces neuroprotection in PD brain pathology. Recent studies show that PD also enhances amyloid beta peptide (AßP) depositions in brain. Keeping these views in consideration in this review, nanowired delivery of monoclonal antibodies to AßP together with ASNC and H3/H4 modulator drugs on PD brain pathology is discussed based on our own observations. Our investigation shows that TiO2 nanowired BF-2649 (1 mg/kg, i.p.) or CLBPT (1 mg/kg, i.p.) once daily for 1 week together with nanowired delivery of monoclonal antibodies (mAb) to AßP and ASNC induced superior neuroprotection in PD-induced brain pathology. These observations are the first to show the modulation of histaminergic receptors together with antibodies to AßP and ASNC induces superior neuroprotection in PD. These observations open new avenues for the development of novel drug therapies for clinical strategies in PD.

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