Chifeng University

Trans-local linkages are central mechanism for peripheral regions to sustain innovation systems, but their spatial configuration and mechanisms remain underexplored. This paper proposes four hypotheses based on the tri-polar framework integrating actor, network, and contextual dimensions, and tests them using co-invention patents from China's high-end equipment manufacturing industry covering 1985-2021. Employing Exponential Random Graph Models, the analysis reveals several key findings: (1) state-owned enterprises and large firms dominate peripheral innovation; (2) the spatial configuration of peripheral innovation is relatively stable; and (3) peripheral cities prioritize cross-hierarchy cooperation, resulting in open network configurations rather than locally closed structures. Overall, peripheral innovation in China is predominantly firm-led, cross-boundary, and selectively oriented toward higher-tier partners. By placing firms at the center of analysis and identifying differentiated types of peripheral cities, this study advances understanding of peripheral regional innovation systems in emerging economies. The findings contribute to the applied geography literature by providing spatially explicit evidence that informs place-based innovation and regional development policy. • Using co-invention patent data from China's high-end equipment manufacturing industry (1985–2021), this study examines the spatial configuration of innovation collaboration in peripheral regions from firm, network, and contextual perspectives. • Innovation activities in peripheral regions are predominantly led by state-owned enterprises and large firms, relying more on cross-regional and cross-hierarchical linkages than on localized clustering. • Peripheral innovation networks display strong relational stability but limited local closure, resulting in open and hierarchically oriented spatial network structures.

IntroductionThis study aimed to explore the efficacy and safety of neoadjuvant immunotherapy combination regimens in locally advanced resectable esophageal squamous cell carcinoma (ESCC), and evaluate the pros and cons of different regimens and their impacts on survival by integrating network meta-analysis (NMA) and real world studies (RWS). ESCC accounts for approximately 90% of global esophageal cancer cases, with over half occurring in China. Although neoadjuvant chemoradiotherapy improves prognosis, unmet clinical needs persist; the optimal neoadjuvant immunotherapy regimen remains controversial. Current large-scale randomized controlled trials (RCTs) suffer from limited sample sizes and fail to adequately reflect the treatment realities of patients in the Chinese real-world setting.MethodsSystematic searches of databases including PubMed, Embase, Web of Science, and CNKI identified eligible RCTs and cohort studies for NMA. Concurrently, clinical data of 113 such ESCC patients who received neoadjuvant immunotherapy combination treatment followed by surgery at National Cancer Centre of China (January 2021–December 2023) were retrospectively collected, with logistic and Cox regression analyses used to assess associations between factors (e.g., MPR, radiotherapy) and survival.ResultNMA results showed Sintilimab plus chemoradiotherapy had the highest pathological complete response (pCR) rate, Camrelizumab plus nab-paclitaxel/platinum performed best in major pathological response (MPR) and radical resection with negative surgical margins (R0 resection) rates, and Sintilimab plus nab-paclitaxel/platinum had the lowest adverse event (AE) incidence. Real-world data revealed a significantly higher MPR rate in the Camrelizumab group than the Tislelizumab group (46.9% vs 12.5%, P = 0.0213). Multivariate analysis indicated MPR and primary tumor T response were independent protective factors for overall survival (OS) and progression-free survival (PFS), while neoadjuvant radiotherapy correlated with poorer OS and PFS.ConclusionNeoadjuvant immunotherapy combinations (notably Cam+nab-TP) exhibit favorable efficacy in this ESCC subtype, and MPR serves as a reliable surrogate endpoint for long-term survival. The survival benefit of radiotherapy requires careful assessment, and clinical decisions should balance efficacy and safety, as these findings provide evidence for individualized treatment.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251174359, identifier CRD420251174359.

Abstract Background Schizophrenia patients often experience mood regulation disorders and perceptual abnormalities, making them susceptible to symptoms such as auditory hallucinations and delusions triggered by environmental stimuli. Architectural lighting, as a core environmental element, can influence the neuroendocrine system through visual pathways via its wavelength and color temperature; however, empirical research on its correlation with patient symptoms is currently scarce in the field of psychiatric treatment. Clinically, patients frequently experience symptom fluctuations due to environmental discomfort, highlighting the urgent need to clarify the intervention value of lighting environments. This would provide a therapeutic basis for the spatial design of psychiatric wards, thereby assisting in optimizing non-pharmacological intervention systems for schizophrenia. Methods Sixty patients with acute schizophrenia were randomly divided into three groups: a warm white light group, a cool white light group, and a natural light group, with 20 patients in each group. The ambient light color parameters were kept stable during the intervention: 3000 K for warm white light and 6500 K for cool white light. The natural light group received primarily diffused daylight during sunny days. The intervention lasted for 8 hours daily for 4 weeks. Perceived symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and emotional state was assessed using the Self-Rating Depression Scale (SDS). Assessments were conducted one day before and one day after the intervention. Data were analyzed using SPSS 26.0 with repeated measures ANOVA. Results After intervention, the PANSS and SDS scores of the three groups of patients were significantly lower than before intervention (intra group comparison). The improvement effect of the warm white light group was significantly better than that of the cold white light group and the natural light group (inter group comparison), and all statistical comparisons were p<.05. Regarding the total PANSS score, the warm white light group decreased from (82.6 ± 7.3) to (51.2 ± 6.8), the cool white light group from (81.9 ± 7.5) to (63.5 ± 7.1), and the natural light group from (83.1 ± 6.9) to (60.3 ± 6.5). In terms of SDS score, the warm white light group decreased from (62.4 ± 5.8) to (41.3 ± 5.2), significantly better than the other two groups. This indicates that the warm white light group was most effective in alleviating perceptual symptoms and negative emotions, while the cool white light group showed the weakest improvement. Discussion Experimental results show that the wavelength and color temperature of warm white light are more in line with the neurophysiological needs of patients. It can regulate the emotional center by inhibiting melatonin secretion and reduce the sensitivity to perceptual abnormalities. Future research can focus on the individualized adaptation of light and color parameters, explore the mechanism of action by combining electroencephalographic indicators, and conduct long-term follow-up to clarify the impact of light and color environment on relapse rate, providing a more precise basis for constructing "therapeutic architectural spaces.".

Pancreatic cancer (PC) is a highly aggressive cancer with poor clinical outcomes. F-box only protein 22 (FBXO22), as an integral part of the SCF E3 ubiquitin ligase complex, has been associated with various cancers, but its role in PC remains underexplored. FBXO22 expression in pancreatic cancer tissues and adjacent normal tissues was analyzed by bioinformatics and validated using quantitative real-time PCR (qPCR). Functional assays, including proliferation, invasion, and apoptosis analyses, were conducted in pancreatic cancer cell lines following FBXO22 overexpression or knockdown. Mass spectrometry-based proteomic profiling was performed to identify potential ubiquitination targets of FBXO22. The interaction between FBXO22 and candidate targets was confirmed by co-immunoprecipitation, western blotting, and ubiquitination assays. The in vivo role of FBXO22 in pancreatic tumor progression was further evaluated using a xenograft model in BALB/c nude mice. FBXO22 was significantly overexpressed in pancreatic cancer tissues compared to adjacent normal tissues. FBXO22 overexpression enhanced pancreatic cancer cell proliferation and invasion, whereas its knockdown suppressed these oncogenic properties. Mass spectrometry identified KLF10 as a potential substrate of FBXO22-mediated ubiquitination. Further experiments confirmed that FBXO22 promotes KLF10 degradation via the ubiquitin-proteasome pathway. Overexpression of KLF10 suppressed pancreatic cancer cell proliferation and induced apoptosis through the TGF-β signaling pathway. In vivo, FBXO22 knockdown significantly inhibited pancreatic tumor growth and increased KLF10 expression. FBXO22 promotes pancreatic cancer progression by mediating KLF10 ubiquitination and degradation, thereby impairing its tumor-suppressive functions. FBXO22 may serve as a potential oncogenic and therapeutic target associated with pancreatic cancer progression.

Hepatic alveolar echinococcosis (HAE), a life-threatening zoonosis, poses formidable surgical challenges when involving critical vasculature. Herein, we reported the periprocedural management dilemmas in radical resection for advanced HAE. A 58-year-old female visited the outpatient department presented with HAE. Imaging examination revealed extensive invasion of the hilum, bile duct, and several hepatic vessels, as well as left adrenal metastasis. The patient underwent right trisegmentectomy with left hepatic vein reconstruction, auto-transplantation, and adrenalectomy, with intraoperative Doppler demonstrating patent portal flow before abdominal closure. However, emergency thrombectomy and transcatheter thrombolysis were performed due to the abrupt occurrence of portal vein thrombosis 3 h after surgery. Despite intervention, the residual liver volume remained insufficient (approximately 28% of the standard liver volume), leading to progressive liver failure. The patient expired from multiorgan failure 9 days after operation. This case underscores not only the critical balance between radical resection and preservation of residual liver function in the surgical management of complex HAE, but also the imperative need to establish a comprehensive postoperative thromboprophylaxis.

Despite generally favorable outcomes, identifying reliable biomarkers remains crucial for managing aggressive subtypes of thyroid cancer. The present study aimed to investigate the association between folate receptor γ (FOLR3) expression and the clinicopathological features of thyroid cancer, and to explore its clinical relevance using bioinformatics and experimental approaches, ultimately assessing its potential value as a diagnostic and therapeutic biomarker. Differential expression analysis of RNA-sequencing data from The Cancer Genome Atlas database was performed to identify the differentially expressed gene FOLR3, followed by standard single-cell analysis. Clinicopathological data from 293 patients with thyroid cancer were collected to investigate pathological characteristics and FOLR3 expression, which was further validated using immunohistochemistry. The functional effects of FOLR3 on the malignant behavior of thyroid cancer cells were assessed using colony formation, Cell Counting Kit-8, scratch wound healing and Transwell invasion assays. FOLR3 expression was significantly higher in normal thyroid tissue compared with cancer tissues (P<0.001). FOLR3 expression level was associated with capsular invasion, perineural invasion, striated muscle invasion and pT stage (all P<0.05). Functional experiments demonstrated that FOLR3 suppressed the proliferation, migration and invasion of TPC-1 cells (all P<0.05). In conclusion, FOLR3 expression is generally low or absent in thyroid cancer, particularly in cases demonstrating pronounced local infiltration, indicating its potential as a diagnostic biomarker for the evaluation of tumor invasiveness. Patients with high FOLR3 expression exhibit a higher survival rate, suggesting its potential prognostic value. FOLR3 inhibits the progression of thyroid cancer by inhibiting the STAT3/MAPK signaling pathways and reprogramming folate metabolism, highlighting its potential as a therapeutic target for thyroid cancer in the future.

BackgroundPalmar hyperhidrosis, characterized by excessive sweating primarily affecting the hands, significantly impairs quality of life and psychological well-being. Although topical agents, iontophoresis, microwave therapy, and sympathectomy are established interventions, real-world treatment patterns and pharmacotherapeutic adequacy among Chinese patients remain poorly delineated.MethodsAn anonymous, questionnaire-based survey was conducted among consecutive patients at a tertiary thoracic surgery clinic in China between March 2023 and October 2024. A total of 363 valid responses were collected and analyzed using SPSS 27.0. Descriptive statistics and multivariable logistic regression were used to evaluate treatment patterns, patient preference, and predictors of treatment selection.ResultsThe study cohort was composed predominantly of individuals with severe disease (87.3% HDSS grade 3–4), and nearly all participants (97.8%) presented with palmar hyperhidrosis. Regarding treatment history, only 38.1% had previously received pharmacotherapy, while 32.6% had utilized Traditional Chinese Medicine (TCM) therapeutic approaches, including TCM, acupuncture, massage and manipulation therapies. Antiperspirants (28.6%) and TCM (25.0%) were the most frequently used prior pharmacotherapies, yet both were associated with limited therapeutic efficacy. According to our survey, owing to high symptom severity, 52.9% had a general knowledge of surgical intervention before the outpatient visit. Primary concerns regarding previous pharmacotherapy included insufficient efficacy and localized adverse effects, particularly skin irritation. Notably, 50.0% of participants remained receptive to future pharmacotherapy, showing a preference for topical formulations (29.3%) and reduced dosing frequency (31.6%). Gender and disease severity were identified as significant determinants of treatment choice. Importantly, prior negative experiences - such as inefficacy and side effects - did not significantly diminish willingness to consider future pharmacologic treatment.ConclusionInadequate management and suboptimal treatment outcomes represent considerable challenges in the care of palmar hyperhidrosis in China. Existing pharmacotherapeutic options are constrained by limited availability, inadequate efficacy, and a narrow range of approved agents - a reality that highlights a critical disconnect with substantial patient demand. These findings underscore an urgent need to accelerate drug development and clinical translation in this field.

The aim of this study was to develop a clinical application model for the rational use of caffeine. Caffeine is related to the incidence of neuro immune gastrointestinal diseases. Coffee consumption needs to be optimized in order to reduce the incidence rate. By using KEEG analysis to explore potential molecular signaling pathways involved in the progression of neurological immune gastrointestinal diseases, and analyzing the details of this signaling Pathway using molecular simulation results, which can support AI system for doctor. The research team designed a controlled experiment to analyze the differences in reward and reinforcement of Brain pleasure/addiction and dopamine related signaling pathways function between multiple groups of people with different coffee drinking habits and a blank control group. The study team used molecular dynamics methods to investigate the signaling route that links coffee with the binding of dopamine receptor D3.AI is used to predict the prevalence of gastric reflux disease. Human experiments have shown a correlation between caffeine intake and gastroesophageal reflux disease. AI algorithm results can provide clinical support, and molecular simulation results are consistent with human experimental results. Caffeine and DRD3 protein have a stable interaction system. The research team elucidated the intermolecular interaction between caffeine and DRD3, and AI algorithms can predict the likelihood of disease occurrence, providing a new strategy for clinical practice. This study has passed ethical approval at Chifeng Cancer Hospital, and the ethical documents for this study have been submitted to the World Health Organization for filing.

ABSTRACTBackgroundSRP72‐associated hereditary bone marrow failure syndrome type 1 (BMFS1) has recently been described and only six families have been reported so far. BMFS1 is an autosomal dominant condition characterized by early‐onset aplastic anemia or pancytopenia in some patients and adult‐onset myelodysplasia in others. This paper presents the clinical and genetic characteristics of a rare case of hereditary bone marrow failure syndrome 1 (BMFS1) and explores its pathogenesis.MethodsBlood samples and clinical data were collected from the proband and his biological parents. Next‐generation sequencing (NGS) was employed to sequence the genes associated with the proband, and the identified variants were subsequently confirmed via Sanger sequencing. Additionally, minigene splicing assays were conducted to assess the functional alterations of SRP72.ResultsA new splicing variant, c.1502+1G>A, was identified in the SRP72 gene through gene sequencing, and this finding was confirmed by Sanger sequencing. Neither parent carried this mutation. Minigene splicing assays revealed an insertion of two bases (AG) at the mRNA level (r.1503‐2_1503‐1insAG), potentially resulting in a premature stop codon (p.Leu502ValfsTer14). According to ACMG guidelines, the variant is classified as “Likely pathogenic”. The c.1502+1G>A mutation in SRP72 is implicated as the potential cause of BMFS1 in this child.ConclusionsOur study identified a novel classical splicing mutation, marking the first report of BMFS1 in China. This case broadens the spectrum of pathogenic variants associated with the SRP72 gene and expands our understanding of its phenotypic manifestations. It also serves as a typical example for early diagnosis and appropriate treatment of BMFS1.