Objective: To develop a prediction model for mild cognitive impairment (MCI) risk among the elderly, so as to provide a tool for MCI early screening. Methods : From July 2022 to September 2024, a multi-stage stratified random cluster sampling method was used to recruit permanent residents aged ≥65 years from the Xinjiang Uygur Autonomous Region as study participants. Data on sociodemographic characteristics, nutritional status, body composition indices, bone mineral density, and handgrip strength were collected through questionnaires and physical examinations. Sarcopenia was defined based on appendicular skeletal muscle index and handgrip strength. MCI was assessed using the Mini-Mental State Examination, with adjustments for educational level. Participants were randomly divided into a training set and a validation set in a 7∶3 ratio. LASSO regression and multivariable logistic regression models were employed to screen for predictors and construct an MCI risk prediction model. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curve and decision curve analysis (DCA). Results: A total of 1 641 participants were surveyed, including 755 males (46.01%) and 886 females (53.99%). The majority of participants were aged 65-<75 years, comprising 1 154 individuals (70.32%). MCI was detected in 517 participants, corresponding to a detection rate of 31.51%. Resultsfrom LASSO regression and multivariate logistic regression analysis showed that residence (rural, OR = 2.323, 95% CI: 1.682-3.210), age (75-<85 years, OR = 1.405, 95% CI: 1.019-1.937; ≥85 years, OR = 3.655, 95% CI: 1.696-7.875), educational level (primary school, OR = 0.341, 95% CI: 0.247-0.472; junior high school, OR = 0.255, 95% CI: 0.160-0.408; high school, OR = 0.286, 95% CI: 0.154-0.531; bachelor's degree or above, OR = 0.120, 95% CI: 0.041-0.351), history of alcohol consumption (yes, OR = 3.216, 95% CI: 2.164-4.779), risk of malnutrition (yes, OR = 1.464, 95% CI: 1.064-2.014), sarcopenia (yes, OR = 3.197, 95% CI: 2.332-4.385), and waist-to-hip ratio (abnormal, OR = 1.540, 95% CI: 1.159-2.048) were identified as predictive factors for MCI among the elderly. In the training set, the area under the ROC curve, sensitivity, and specificity were 0.788, 0.719, and 0.712, respectively. In the validation set, the corresponding values were 0.784, 0.913, and 0.542, respectively. DCA demonstrated that the model provided a higher clinical net benefit for predicting MCI risk when the risk threshold probability ranged from 0.124 to 0.764. Conclusion The prediction model developed in this study demonstrates good discriminative ability and clinical utility, indicating its substantial value for predicting the MCI risk among the elderly.

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer-related mortality worldwide. Despite therapeutic advancements over recent decades, the prognosis for patients with metastatic CRC (mCRC) remains poor. Approximately 2%-4% of mCRC cases exhibit human epidermal growth factor receptor 2 (HER2) amplification or overexpression, defining a distinct molecular subtype. This HER2-positive status is strongly associated with primary resistance to anti-epidermal growth factor receptor (EGFR) therapies, which are the standard of care for patients with RAS wild-type tumors. Beyond its well-established role in breast and gastric cancers, HER2 has emerged as a pivotal biomarker and actionable therapeutic target in mCRC. However, selecting appropriate treatment strategies remains challenging due to patient heterogeneity and diverse molecular subtypes. This review systematically summarizes the molecular biology, diagnostic strategies, and advances in targeted therapies for HER2-positive mCRC. On the diagnostic front, we discuss the applications of immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and circulating tumor DNA (ctDNA) detection technologies. We highlight discrepancies in diagnostic criteria across key clinical trials—such as HERACLES, DESTINY, and MOUNTAINEER—underscoring the urgent need for standardized, CRC-specific definitions to ensure consistent patient selection and comparability of efficacy data across studies. Although NGS enables comprehensive genomic profiling, its cost-effectiveness relative to traditional methods must be carefully considered. Therapeutically, we summarize clinical trial data for HER2-directed agents, including tyrosine kinase inhibitors (TKIs) such as tucatinib and lapatinib, monoclonal antibodies like trastuzumab, bispecific antibodies, and antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan. We review dual-targeting strategies and note recent FDA approvals that represent significant milestones in second-line treatment. Additionally, we explore the potential of combining immune checkpoint inhibitors with HER2-targeted therapies to enhance antitumor immunity through mechanisms including antibody-dependent cellular cytotoxicity (ADCC) and modulation of the tumor microenvironment. ADCs enable precise delivery of cytotoxic payloads, reducing off-target toxicity while effectively inhibiting oncogenic pathways. A substantial portion of this review is dedicated to dissecting the molecular mechanisms underlying primary and acquired resistance to HER2-targeted therapies—persistent challenges that limit clinical benefit. These mechanisms include reactivation of downstream signaling pathways such as PI3K/AKT/mTOR and MAPK, concurrent mutations in genes like KRAS or BRAF, and alterations in HER2 expression that compromise treatment efficacy. For instance, specific HER2 mutations (e.g., L755S) can reduce drug binding affinity, while ctDNA monitoring facilitates early detection of emerging resistance clones during disease progression, thereby enabling timely therapeutic adjustments. Tumor heterogeneity and dynamic interactions with the microenvironment further complicate resistance patterns observed in clinical practice. HER2-targeted therapy represents a new frontier in precision oncology for mCRC, offering renewed hope for improving patient outcomes. Realizing this potential will require continued optimization of diagnostic algorithms and treatment workflows. Future efforts must focus on overcoming resistance, validating liquid biopsy approaches for dynamic monitoring, and establishing unified clinical guidelines. HER2 has become an essential biomarker for stratifying mCRC patients beyond traditional RAS and BRAF status, underscoring the shift from empiric treatment to biomarker-driven precision medicine. International, multidisciplinary collaboration will be critical to validate emerging biomarkers and refine treatment algorithms globally.

Numerous techniques for C2 screw fixation have been recently reported. However, concerns remain regarding the risk of spinal cord or vertebral artery injury and inadequate biomechanical stability. To our knowledge, the specific transforaminal “in-out-in” screw fixation technique has not been previously reported. This study aimed to investigate the feasibility and preliminary clinical outcomes of a transforaminal “in-out-in” multi-cortical purchase screw for posterior C2 screw fixation. Between October 2022 and March 2023, 10 patients underwent posterior atlantoaxial internal fixation. All patients had severe hypoplasia of the C2 pedicle on at least one side, precluding the use of standard C2 pedicle screws. A transforaminal “in-out-in” screw was used as an alternative. No spinal cord injury, vascular injury, or other major complications were observed. No implant failure was noted at the final follow-up. In conclusion, the transforaminal “in-out-in” screw may achieve rigid three-column fixation with multiple cortical purchases. It represents a safe and effective alternative for posterior C2 fixation in patients with severely narrow C2 pedicles where traditional pedicle screw placement is not feasible.

Endoscopic full-thickness resection (EFTR) is a minimally invasive technique that is increasingly used for gastrointestinal stromal tumors (GISTs) originating from the muscularis propria. Despite its advantages over conventional surgery, such as complete tumor resection and faster recovery, EFTR faces challenges related to its efficacy, safety, and feasibility, particularly in gastric GISTs. By summarizing the literature published over the past decade, this review provides a comprehensive overview of the clinical outcomes of EFTR and the evolution of defect closure devices.

Objective To provide a scientific basis for vector prevention and control in port areas, vector monitoring has been conducted continuously to characterize the composition, density, and seasonal fluctuations of vectors across 21 port-areas of Shandong province from 2017 to 2023. Methods In accordance with the Regional Vector Monitoring Plan for Frontier Ports, vector surveillance of mosquitoes, flies, cockroaches, rodents, and other disease vectors was performed. Data were analyzed to describe vector community composition and identify seasonal fluctuations. Results A total of 601 rodents belonging to 1 family, 4 genera, and 4 species were captured. Three dominant rodent species inhabit port areas. In addition, 88 104 mosquitoes were captured and classified into 3 subfamilies, 4 genera, and 12 species; 38 959 flies were trapped and classified into 8 families,31 genera, and 51 species, including 9 dominant fly species in port-areas; and 54 672 captured cockroaches were classified into 2 families,4 genera, and 4 species, with Blattella germanica as the dominant species. Conclusions Significant vector community changes(P＜0.005)have been identified after the epidemic. To improve the pertinence and efficacy of port health quarantine work, continuous and strong attention should be paid to vector compositions and population densities at Shandong ports.

ObjectiveTo investigate the mechanism by which activation of α7nicotinic acetylcholine receptors （α7nAChR） optimizes brown adipose tissue （BAT） thermogenesis in obese mice. MethodsObesity was induced in C57BL/6J mice via a high-fat diet. Fifty 8-week-old mice were randomly assigned to five groups： low-fat diet （Control）， high-fat diet （HFD）， high-fat diet plus a β3-adrenergic receptor agonist （HFD+β3）， high-fat diet plus a β3-adrenergic receptor agonist and an α7nAChR selective agonist （HFD+β3+GTS-21）， and high-fat diet plus a β3-adrenergic receptor agonist and an α7nAChR selective antagonist （HFD+β3+α-BGT）. Haematoxylin and eosin （HE） staining was used to evaluate BAT morphology. Transmission electron microscopy was performed to assess mitochondrial number and lipid droplet morphology in adipocytes. ELISA was used to measure levels of tumour necrosis factor-α （TNF-α）， interleukin（IL）-1β，IL-10， transforming growth factor-β （TGF-β）， cyclic adenosine monophosphate （cAMP）， and norepinephrine （NE）. RT-qPCR was conducted to determine mRNA expression levels of vascular endothelial growth factor A （VEGF-A）， nitric oxide synthase 2 （NOS2）， arginase 1 （Arg1）， uncoupling protein 1 （UCP1）， PR domain-containing protein 16 （PRDM16）， and peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α） in BAT. Immunohistochemistry was used to detect macrophage markers （CD31， CD86， and CD206）. Protein expression levels of UCP1， α7nAChR， nuclear factor-κB p65（NF-κB p65）， phosphorylated Janus kinase 2 （p-JAK2）， and phosphorylated signal transducer and activator of transcription 3 （p-STAT3） were analyzed by Western blot. ResultsCompared with the Control group， the HFD group showed enlarged lipid droplets and reduced mitochondrial numbers in adipocytes， accompanied by increased TNF-α and IL-1β and decreased IL-10， TGF-β， Arg1， and VEGF-A （all P<0.01）. Compared with the HFD+β3 group， the HFD+β3+GTS-21 group showed a smaller lipid droplet area and a higher mitochondrial number， along with reduced levels of pro-inflammatory factors， NOS2， and NF-κB p65， and increased levels of anti-inflammatory factors， Arg1， and phosphorylation of JAK2 and STAT3 （all P<0.01）. ConclusionActivation of α7nAChR in combination with a β3-adrenergic receptor agonist effectively enhances thermogenesis， alleviates local adipose tissue hypoxia， and shifts the local inflammatory phenotype toward an M2-like state， thereby reducing inflammation in brown adipose tissue and improving its thermogenic capacity.

BackgroundBoth modified Suanzaoren Decoction and estazolam serve as effective treatments for chronic insomnia disorder （CID）. Default mode network （DMN） dysfunction is recognized as the primary pathophysiological mechanism underlying CID. However， it remains unclear whether the two treatments exert their therapeutic effects via convergent modulation of DMN functional connectivity. ObjectiveTo investigate the convergent remodeling characteristics of bidirectional effective connectivity （EC） of core DMN nodes with both the intra-network and the remaining whole-brain regions in CID patients with Yin-deficiency and fire-hyperactivity syndrome following the treatment with modified Suanzaoren Decoction or estazolam， so as to provide neuroimaging evidence for the convergent neural mechanisms underlying the therapeutic effects of both therapies in treating CID. MethodsEighty-two patients diagnosed with CID according to the International Classification of Sleep Disorder， third edition （ICSD-3） were consecutively recruited from the outpatient clinic of the Inner Mongolia Autonomous Region Mental Health Center from October 2020 to September 2023. Based on treatment preference， patients were assigned to receive a 6-week intervention in either the modified Suanzaoren Decoction group （n=52） or the estazolam group （n=30）. Ultimately， 66 patients completed follow-up assessments （modified Suanzaoren Decoction group， n=41； estazolam group， n=25）. All CID patients underwent resting-state functional magnetic resonance imaging scanning before and after treatment. Core DMN nodes including medial prefrontal cortex （mPFC）， bilateral inferior parietal lobule （IPL）， and precuneus （PCUN） were selected as seed regions. Granger causality analysis （GCA） was employed to assess bidirectional EC between the seed regions and both the other intra-DMN nodes and the remaining whole-brain regions. Hepatic and renal function indices were detected pre- and post-treatment to evaluate the safety profiles of both treatments. ResultsAt baseline， significant between-group differences were identified in EC from the left IPL to the left middle fronto-orbital gyrus/gyrus rectus （t=5.24， Z=4.84， voxel-level P<0.001， cluster-level P<0.05， GRF-corrected）， with the modified Suanzaoren Decoction group exhibiting stronger EC than the estazolam group. No significant between-group differences were observed in EC between other core DMN nodes and remaining whole-brain regions （P>0.05）. Within-group pre- to post-treatment comparisons demonstrated consistent connectivity alterations in both groups. Specifically， EC from the left IPL to the supplementary motor area （SMA） decreased after treatment （modified Suanzaoren Decoction group： t=-6.28， Z=5.208； estazolam group： t=-5.58， Z=4.425）. Conversely， EC from the SMA to the left IPL increased （modified Suanzaoren Decoction group： t=5.89， Z=4.968； estazolam group： t=6.15， Z=4.720）. Furthermore， both groups demonstrated reduced EC from the PCUN to the left IPL （modified Suanzaoren Decoction group： t=-5.85， Z=4.94； estazolam group： t=-5.75， Z=4.515）， and elevated EC from the left IPL to the PCUN （modified Suanzaoren Decoction group： t=5.29， Z=4.579； estazolam group： t=4.55， Z=3.826） （voxel-level P<0.001， cluster-level P<0.05， GRF-corrected）. No significant pre- to post-treatment differences were observed in hepatic or renal function indices in either group （P>0.05）. ConclusionIn CID patients with Yin-deficiency and fire-hyperactivity syndrome， both modified Suanzaoren Decoction and estazolam induce convergent bidirectional remodeling of EC between the left IPL and the SMA and the PCUN. ［Funded by Natural Science Fund Project of Inner Mongolia Autonomous Region （number， 2019MS08099）； ClinicalTrials.gov number， NCT06452953］

OBJECTIVES: To evaluate the association of GGN repeat polymorphism of androgen receptor (AR) with ovarian reserve and ovarian response in controlled ovarian stimulation (COS). METHODS: This genetic association study was conducted among a total of 361 women aged ≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university-affiliated IVF center. GGN repeat in the AR gene was analyzed with Sanger sequencing. The primary endpoint was the number of antral follicle counts (AFCs), and the secondary endpoints were stimulation days, total dose of gonadotropin (Gn) used, total number of retrieved oocytes, ovarian sensitivity index, and follicular output rate. RESULTS: The GGN repeat in exon 1 of the AR gene ranged from 13 to 24, and the median repeat length was 22. Based on the genotypes (S for GGN repeats <22, L for GGN repeats ≥22), the patients were divided into 3 groups: SS, SL, and LL. Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL (adjusted β=1.8, 95% CI: 0.2-3.4, P=0.024) and group LL (adjusted β=1.5, 95% CI: 0.2-2.7, P=0.021). No significant difference was observed in the number of AFCs between group SL and group LL (P>0.05). Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups, either before or after adjusting for confounding factors (P>0.05). CONCLUSIONS GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women, indicating that AR gene polymorphisms may affect ovarian reserve.
Adult ; Female ; Humans ; Genotype ; Ovarian Follicle/cytology* ; Ovarian Reserve/genetics* ; Ovulation Induction/methods* ; Polymorphism, Genetic ; Receptors, Androgen/genetics* ; East Asian People/genetics*

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.