ObjectiveAs a common lifestyle habit, alcohol consumption has a controversial association with the onset of Parkinson’s disease (PD). To demonstrate the correlation between alcohol consumption and PD and to identify associated genes, we integrated findings from clinical surveys, genomics, transcriptomics, and animal experiments. MethodsWe investigated the alcohol consumption rates (including both before and after disease onset) among 244 PD patients in China and 177 PD patients from the U.S. NHANES database. Mendelian randomization (MR) analysis was performed using genome-wide association study (GWAS) data for three alcohol-related traits and seven PD-related datasets from the MRC IEU OpenGWAS database. Transcriptomic data from the substantia nigra of PD patients were obtained from three GEO datasets (GSE7621, GSE20141, and GSE49036) to analyze RIT2 gene transcription. Finally, three groups of animal experiments (water/20% ethanol/20% liquor, with 4 C57BL/6J mice per group) were conducted to examine changes in brain RIT2 gene expression and transcriptomic profiles following alcohol consumption. ResultsThe alcohol consumption rates among PD patients in China and the U.S. (9%-18.87%) were significantly lower than the general population rates of 15%-45% in their respective regions (P<0.001), suggesting a possible negative association between alcohol consumption and PD. Subsequently, in 21 bidirectional MR analyses using 3 alcohol-related GWAS datasets and 7 PD-related GWAS datasets, the forward MR analyses (alcohol intake as exposure, PD as outcome) yielded 12 negative associations (OR_IVW<1) and 9 positive associations (OR_IVW>1). Among these, only two negative associations reached statistical significance: alcohol intake frequency (OR_IVW=0.75, 95% CI: 0.60-0.93, P=0.010) and alcohol consumption (OR_IVW=0.20, 95% CI: 0.05-0.83, P=0.026). The forward MR analysis (alcohol intake→PD) identified 235 SNPs, annotated to 316 genes, while the reverse MR analyses (PD→alcohol intake) identified 37 SNPs, annotated to 53 genes. Notably, only the RIT2 gene appeared in both the forward and reverse MR analyses (alcohol intake→PD: rs28597806, rs8083110; PD→alcohol intake: rs4588066). RIT2 is selectively expressed in the human brain (FPKM: 5.259±2.103), with low or no expression in peripheral tissues (FPKM: <1). Analysis of three human substantia nigra transcriptomic datasets revealed a decreasing trend in RIT2 gene expression in PD patients (GSE20141 array signal: 3.49±1.23 vs. 2.33±0.87, P=0.044). Animal experiments demonstrated that administration of 20% ethanol or 20% liquor (approximately 8% ethanol) stimulated a >2-fold upregulation of RIT2 gene expression in the mouse brain. Furthermore, transcriptomic sequencing revealed that the two alcohol-treated groups exhibited 96 (20% ethanol vs. water control) and 4 (20% liquor vs. water control) differentially expressed genes, respectively, indicating that low-dose alcohol consumption can achieve RIT2 upregulation while minimizing impact on other brain genes. In addition to its anti-infective effects, low-dose alcohol consumption primarily influences signaling pathways related to neurodegenerative diseases such as PD and Prion diseases. ConclusionAlcohol consumption is generally considered as a harmful lifestyle habit. However, some studies have also shown a lower risk of mortality among individuals who consume low doses of alcohol (100 g/week of ethanol) or drink occasionally. Currently, one of the research focuses on alcohol consumption is whether the human body can benefit from low-dose alcohol intake. This study provides new evidence supporting a negative association between alcohol consumption and PD, and for the first time, through MR analysis, identifies the RIT2 gene as a potential mediator of the effect of alcohol consumption on PD. RIT2 is selectively expressed in the human brain. Building upon existing evidence indicating downregulated RIT2 gene expression in PD pathogenesis, our experiments confirm that low-dose alcohol consumption can upregulate RIT2 expression in the brain. In brief, alcohol consumption may suppress the pathogenesis of PD by upregulating RIT2 expression in the substantia nigra. China is facing a serious problem of population aging. This study offers important insights for long-term PD prevention and treatment strategies, with the aim of benefiting more potential PD patients through lifestyle modifications, thereby improving the quality of life of the aging population and reducing the economic burden on healthcare.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

Objective: To analyze the demographic evolution of China over the forthcoming decade (2026-2035) and to systematically evaluate its potential implications for voluntary blood donation practices and the equilibrium of clinical blood supply and demand. Methods: Leveraging comprehensive blood collection and utilization data from 2021 to 2025 at the national, provincial (Shandong), and municipal (Zibo) levels, we identified and examined critical determinants influencing blood management systems. The DeepSeek-V3.2 large language model was deployed to project future population age structures, and to generate quantitative estimates for hospitalization volumes, clinical blood requirements, available blood supply, and donation frequencies for the target years 2030 and 2035, thereby furnishing an evidence base for strategic planning and priority-setting. Results: DeepSeek-derived projections indicate that the proportion of China's population aged 60 years and above will surpass 27% (370 million/1 380 million) by 2030 and exceed 30% (400 million/1 350 million) by 2035, signaling a marked acceleration in population aging. This demographic shift is projected to reduce the proportion of the national population eligible to donate blood from 59.2% (835 million out of 1.41 billion) to 52% (710 million out of 1.36 billion), while the demand for blood is expected to increase by 87.8% relative to 2024, rising from 26.927 million units to 50.56 million units. Sustaining blood supply-demand balance will necessitate progressive annual increases in donation rates. Under prevailing policy frameworks, the required blood donation rate among the eligible population in Shandong Province would need to rise by 122.57% by 2035 [from 20.07‰ (1.1641 million person-times/58 million people) to 44.67‰ (2.189 million person-times/49 million people)] to potentially satisfy projected clinical requirements. Conclusion: By integrating DeepSeek-V3.2, AI predictive models, and blood donation incentive measures, it is possible to monitor population demographics, forecast clinical blood demand, manage blood supplies, and ensure the long-term sustainability of clinical blood availability. It must be acknowledged, however, that the present analysis is constrained by a limited data foundation (comprising only five annual observation points); accordingly, the projections should be interpreted as directional trend indicators or methodological illustrations rather than definitive quantitative forecasts.

Lung cancer constitutes the most prevalent and lethal malignant tumor in China. Approximately 85% of lung cancer diagnoses correspond to the non-small cell histological subtype [non-small cell lung cancer (NSCLC)]. Despite surgery being the mainstay for early-stage disease, postoperative recurrence remains high and adjuvant chemotherapy offers limited benefit. In recent years, targeted therapy has demonstrated substantial advantages in driver mutation-positive NSCLC. To this end, the Lung Cancer Medical Education Committee of the Chinese Medical Education Association developed guidelines based on a systematic review of evidence through November 2025, using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach and a modified Delphi method. Focusing on epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and addressing ROS proto-oncogene 1 (ROS1), B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutation, and mesenchymal-epithelial transition factor (MET) exon 14 (METex14) skipping, the guideline covers molecular testing, neoadjuvant/adjuvant therapy, perioperative strategies, minimal residual disease monitoring, and postoperative surveillance. It defines testing requirements, specifies stage-directed and subtype-specific treatments, and standardizes minimal residual disease monitoring. These recommendations emphasize precision and feasibility to improve survival and quality of life.

ObjectiveStroke remains the leading cause of acquired disability in adults worldwide, imposing a substantial socioeconomic burden on patients, families, and healthcare systems. Among the various neurological deficits caused by stroke, motor dysfunction——particularly contralateral hemiplegia——is the most common and debilitating consequence, and it predominantly results from damage to the cortical motor conduction pathways. When motor cortex neurons or their projecting fibers are damaged, the distal axons and their associated myelin sheaths undergo a series of progressive, programmed degeneration, fragmentation, and eventual phagocytic clearance. This pathological process is termed Wallerian degeneration (WD). However, the temporal progression of WD following ischemic stroke and the associated alterations in the local glial microenvironment remain incompletely understood. The present study was designed to systematically elucidate the time course of corticospinal tract (CST) axonal WD after ischemic stroke in mice, and to simultaneously characterize the dynamic pathological changes of astrocytes, microglia, oligodendrocyte lineage cells, and myelinating oligodendrocytes during the WD process. MethodsEight-week-old male C57BL/6J mice were randomly assigned to control and ischemic stroke groups. A focal cortical ischemic stroke model was established in the right sensorimotor cortex using the photothrombotic method. This method induces localized intravascular thrombosis in the target cortical region through precisely controlled interaction between the photosensitizer and laser light of specific wavelength. At day 1 post‑surgery, 2,3,5-triphenyltetrazolium chloride (TTC) staining was performed to evaluate infarct volume, hematoxylin and eosin (HE) staining for histopathological examination, and Nissl staining for assessment of neuronal injury. For axonal degeneration time-course analysis, rAAV-CAG-mCherry anterograde viral tracing was employed to specifically label CST neurons. Cervical spinal cord sections at the CST region were collected at day 3, 5, 7, 14, and 60 post-injury. Morphological changes of mCherry-positive CST fibers were observed under fluorescence microscopy, and the fluorescence signal area fraction within the defined region was quantitatively analyzed to evaluate the dynamic process of axonal degeneration. For glial response assessment, immunofluorescence staining against Iba1 (microglia), GFAP (astrocytes), Olig2 (oligodendrocyte lineage cells), and APC (myelinating oligodendrocytes) was performed at day 7, 14, and 60 post‑surgery. The numbers of positive cells were counted to quantitatively analyze the dynamic changes in each glial population at different time points after ischemia, thereby revealing the evolution of the glial microenvironment during WD. ResultsThe photothrombotic method stably and reliably established an ischemic brain injury model confined to the sensorimotor cortex. Viral tracing revealed that the proportion of mCherry‑positive CST fibers was significantly reduced at day 7 after ischemic injury to the neuronal soma. Immunofluorescence staining demonstrated that during WD, the numbers of microglia and astrocytes in the CST region were significantly increased, whereas the numbers of oligodendrocyte lineage cells and myelinating oligodendrocytes showed no significant changes. ConclusionWD of CST axons is observed at day 7 post-ischemic stroke in a delayed manner. This degenerative process selectively activates microglia and astrocytes, while leaving the number of oligodendrocyte lineage cells largely unaffected.

Objective:To prepare decellularized extracellular matrix (dECM)-gelatin methacryloyl (GelMA) composite hydrogels and to study their effects on hepatocyte proliferation.Methods:Hepatic dECM was prepared by elution, and GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels were prepared by pepsin solubilization. The morphology of normal liver and dECM liver was observed by eyes and scanning electron microscopy using hematoxylin-eosin, Sirius red and periodate-Schiff staining, respectively. The internal structure of the dECM-GelMA composite hydrogels was observed by scanning electron microscopy, and the pore diameter was measured. Liver HL-7702 cells were co-cultured with GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels, and the cell proliferation viability was determined by cell counting kit-8. The expression of proliferating cell nuclear antigen (PCNA), Wnt family protein 5a (Wnt5a), β-catenin, extracellular-regulated protein kinase 1/2 (ERK1/2) and phosphorylated ERK1/2 (p-ERK1/2) were detected by Western blotting. Comparisons were made using independent sample t-test or one-factor analysis of variance. Results:After decellularization, the hepatocyte morphology showed rounded depressions, and the extracellular matrix structure was intact. The GelMA hydrogel and 10%, 30% and 50% dECM-GelMA composite hydrogels showed inernally porous structures. The pore diameter increased from (3.06±1.35) μm in the GelMA hydrogel to (16.01±4.02) μm in the 50% dECM-GelMA composite hydrogel. On the 3rd, 5th and 7th day, the relative cell proliferation was higher in the 50% dECM-GelMA composite hydrogel group than that in the GelMA hydrogel group (1.89±0.04 vs 1.53±0.01, 9.36±0.04 vs 3.89±0.09, 7.15±0.27 vs 4.89±0.15, all P<0.05). The relative expression levels of PCNA, Wnt5a, β-catenin, and p-ERK1/2/ERK1/2 proteins in the 50% dECM-GelMA composite hydrogel group were higher than those in the GelMA hydrogel group (2.14±0.04 vs 1.00±0.03, 2.36±0.09 vs 1.00±0.08, 1.45±0.03 vs 1.00±0.04, 1.43±0.04 vs 1.00±0.01, all P<0.05). Conclusions:A dECM-GelMA composite hydrogel can be prepared, which may promote hepatocyte proliferation by upregulating the phosphorylation of ERK1/2 and activating Wnt/β-catenin signaling pathway.

Objective To explore the application value of musculoskeletal ultrasound(MSUS)in grading acute gastrocnemius muscle injuries.Methods A retrospective analysis was conducted on ultrasound images of 291 patients who presented with sudden calf pain and suspected acute gastrocnemius muscle injury in the General Hospital of Central Theater Command from March 2019 to July 2024.The images were independently reviewed and assessed by three ultrasound doctors with different qualifications to determine the presence and grade of gastrocnemius muscle injury.The consistency of grading results among three doctors was compared.The diagnostic results of three doctors were summarized.Then,the diagnostic results of 29 patients who underwent routine MRI scans were compared with those of MSUS,and the agreement between the two imaging modalities was assessed using the Kappa test.Results Among the 291 patients,171 cases(58.8%)were diagnosed with gastrocnemius muscle injury,including 55 cases(32.2%)with grade Ⅰ,109 cases(63.7%)with grade Ⅱ,and 7 cases(4.1%)with grade Ⅲ.There were 159 cases(93.0%)of unilateral medial head injury,10 cases(5.8%)of unilateral lateral head injury,and 2 cases(1.2%)of bilateral medial and lateral head injury.Compared with patients without gastrocnemius muscle injury,patients with gastrocnemius muscle injury were older(P<0.05),with no significant difference in gender and laterality(P>0.05).No significant differences in baseline characteristics were found among patients with different grades of injury(P>0.05).The three doctors diagnosed 173(59.5%),171(58.8%),and 171(58.8%)cases of injury,respectively,with an inter-class correlation coefficient(ICC)of 0.947(P<0.001).Among 29 patients who underwent MRI,the diagnostic agreement between MRI and ultrasound for grade Ⅰ,Ⅱ and Ⅲ injury was 8(27.6%),18(62.1%)and 3(10.3%)for MRI;and 9(31.0%),17(58.6%)and 3(10.3%)for MSUS,respectively,with a Kappa value of 0.808(P<0.001).Conclusions MSUS is effective for assessing the grade of acute gastrocnemius muscle injury,and shows high diagnostic consistency among doctors with different qualifications.It is recommended as the preferred method for diagnosing gastrocnemius muscle injury.

Objective To explore the relationship between dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)and clinical pathological features of invasive breast cancer and lymphovascular invasion(LVI).Methods Imaging and clinical pathological data were retrospectively collected from 508 patients with invasive breast cancer who underwent breast DCE-MRI at the First Medical Center of Chinese PLA General Hospital from January 2019 to August 2021.Patients were divided into the LVI-positive(LVI+)group(n=79)and LVI-negative(LVI-)group(n=429)based on postoperative pathological results.Univariate and multivariate logistic regression analyses were used to identify risk factors for LVI.Results Compared with LVI-group,LVI+group had a higher proportion of patients aged<45 years(44.3%vs.27.0%,P=0.002),non-mass-like enhancement(NME)(31.7%vs.17.7%,P=0.004),Ki-67 expression rate(40.0%vs.30.0%,P<0.001),high Ki-67 expression(94.9%vs.78.1%,P=0.001),Luminal B subtype(76.0%vs.60.1%,P=0.008),and positive axillary lymph nodes rate(72.2%vs.31.5%,P<0.001),while the proportion of Luminal A subtype was lower(2.5%vs.21.5%,P<0.001).Univariate and multivariate logistic regression analyses showed that age≥45 years(OR=0.468,95%CI 0.280-0.783,P=0.004)was an independent protective factor for LVI,while NME(OR=1.987,95%CI 1.126-3.444,P=0.016)was an independent risk factor.Compared with Luminal A subtype,patients with Luminal B subtype(OR=10.482,95%CI 3.164-64.923,P=0.001),HER-2 overexpression subtype(OR=11.571,95%CI 2.755-79.341,P=0.003)and triple-negative subtypes(OR=8.433,95%CI 1.985-57.908,P=0.009)had a higher risk of LVI.Conclusions Age≥45 years is an independent protective factor for LVI,while NME is an independent risk factor.Among molecular subtypes,patients with Luminal B,HER-2 overexpression and triple-negative subtypes have a higher risk of LVI compared with the Luminal A subtype.

Objective To investigate the characteristics of thickness changes in peripapillary retinal nerve fiber layer(pRNFL)and identify related risk factors in patients with Moyamoya disease(MMD).Methods A retrospective study was conducted on 150 MMD patients(150 eyes)aged 6-65 years admitted to the Neurosurgery Department of the Fifth Medical Center,Chinese PLA General Hospital from May 2016 to December 2023(observation group),and 150 age-matched healthy volunteers(150 eyes)from the hospital's ophthalmology outpatient department(control group).Both groups were subdivided into pediatric(≤18 years),young adult(18-40 years),and middle-aged(40-65 years)subgroups.The pRNFL thickness in four quadrants was measured by optical coherence tomography(OCT):superior(pRNFL-Sup),inferior(pRNFL-Inf),nasal(pRNFL-Nas),temporal(pRNFL-Tmp),and average thickness(pRNFL-Avg).General clinical data and pRNFL thickness were compared between two groups.Univariate and multivariate logistic regression analyses were performed to identify risk factors for pRNFL thinning in MMD patients.The cohort was randomly divided into training(n=210)and validation(n=90)sets at a 7:3 ratio.A predictive model for pRNFL thinning in MMD patients was constructed based on logistic regression results.Model performance was evaluated using the area under the receiver operating characteristic curve(AUC),and clinical utility was assessed via decision curve analysis.Results Compared with control group,MMD patients exhibited significantly reduced pRNFL-Avg,pRNFL-Sup,pRNFL-Tmp,and pRNFL-Inf thickness(P<0.05 or P<0.001),while pRNFL-Nas showed no significant difference(P>0.05).In the pediatric subgroup,pRNFL-Avg and pRNFL-Inf were thinner(P<0.05).In the young adult subgroup,pRNFL-Avg and pRNFL-Sup were reduced(P<0.001 or P<0.05).In the middle-aged subgroup,pRNFL-Avg,pRNFL-Sup,pRNFL-Inf,and pRNFL-Tmp were all thinner(P<0.05 or P<0.001).Multivariate logistic regression identified visual field defects(OR=15.28,95%CI 2.95-79.10),disease duration(OR=1.11,95%CI 1.05-1.18),and the number of involved cerebral vessels(OR=1.49,95%CI 1.01-2.22)as independent risk factors for pRNFL thinning.The predictive model achieved AUC of 0.94(95%CI 0.91-0.97)and 0.95(95%CI 0.91-0.99)in the training and validation sets,respectively.Decision curve analysis confirmed the model's favorable clinical net benefit.Conclusion Thinning of pRNFL was observed in Moyamoya disease patients with visual field defects,disease duration,and cerebral vascular involvement identified as independent risk factors for pRNFL atrophy.

Objective To report a case of tibial synovial sarcoma and review relevant literature to enhance understanding of this disease.Methods The clinical data of a patient with tibial synovial sarcoma treated at Kaifeng Central Hospital were retrospectively analyzed.A literature search was conducted in domestic and international databases,including China National Knowledge Infrastructure(CNKI),Wanfang Data,PubMed,Web of Science,and Embase,up to July 2024.Relevant literature was comprehensively reviewed to summarize the imaging and pathological characteristics,treatment,and prognosis of synovial sarcoma.Results A 29-year-old female patient was admitted with left lower extremity pain.X-ray examination revealed a proximal tibia space-occupying lesion suggestive of malignancy,and a mid-tibial space-occupying lesion considered benign.Contrast-enhanced computed tomography(CT)and plain magnetic resonance imaging(MRI)of the proximal tibial lesion also suggested malignancy.Ultrasound-guided biopsy of the proximal tibial tumor revealed a poorly differentiated malignant tumor.Immunohistochemistry results indicated monophasic synovial sarcoma,requiring genetic testing for definitive diagnosis.The patient underwent wide resection of the proximal left tibial malignancy with tumor-type artificial joint replacement,combined with curettage and bone cement filling for the left mid-tibial lesion under anesthesia.Postoperative pathology of space-occupying lesions in the proximal tibia confirmed monophasic synovial sarcoma,and fluorescence in situ hybridization(FISH)demonstrated a rupture of the synovial sarcoma translocation gene(SYT)(i.e.,SS18 positive).There was no recurrence or metastasis found in the patient during the reexamination 6 months after postoperative chemotherapy.As of July 2024,15 cases of genetically confirmed primary intraosseous synovial sarcoma have been reported internationally.Symptoms included pain and swelling,with a medical history of 1-2 years.The X-ray and CT findings showed osteolytic destruction with bone cortical discontinuity.In 13 cases,the intraosseous masses extended to the extraosseous area;in 2 cases,punctate calcifications were detected within the masses.Plain MRI scan showed iso-signal or hypo-signal on T1WI and hyper-signal,iso-signal,and hypo-signal on fat-suppressed T2WI,and enhanced MRI scan demonstrated heterogeneous enhancement.Pathological examination showed spindle-shaped cells under microscopy.Immunohistochemistry results showed positive epithelial membrane antigen(EMA),broad-spectrum cytokeratin(AE1/AE3),Ewing's sarcoma marker(CD99),and transducin-like enhancer of Split 1(TLE1).Twelve patients underwent surgical treatment;6 patients received adjuvant chemotherapy after surgery,of whom 4 developed local recurrence or distant metastasis at initial diagnosis,and 3 died during follow-up.Among the 6 patients who did not receive adjuvant chemotherapy,3 suffered from recurrence or distant metastasis.Conclusions Primary intraosseous synovial sarcoma is a rare malignant tumor with non-specific clinical manifestations.Imaging features typically include osteolytic destruction and intraosseous masses extending extraosseously,suggesting an intraosseous origin.Pathology and immunohistochemistry aid diagnosis,but definitive confirmation relies on further genetic testing.At present,the main treatment regimens for synovial sarcoma involve comprehensive therapies such as surgery and adjuvant chemotherapy,and the prognosis of patients is poor.