Objective To explore the connection between immune-related plasma proteins and Parkinson's disease.Methods By analyzing genome-wide association study data of 4907 immune-related plasma proteins,we assessed their direct impact on the risk of Parkinson's disease.Single-nucleus RNA sequencing data were also utilized for protein expression analysis.Results Four im-mune-related proteins,cerebral dopamine neurotrophic factor(CDNF),cathepsin B(CTSB),im-munoglobulin G Fc receptor 2a(FCGR2A),and hemoglobin beta subunit(HBB),were identified to be associated with the risk of Parkinson's disease.Among them,increased expression levels of CDNF,CTSB and HBB were found to decrease the risk(OR=0.871,95％CI:0.779-0.973,P=0.015;OR=0.835,95％CI:0.758-0.920,P=0.001;OR=0.735,95％CI:0.631-0.857,P=0.001),whereas increased level of FCGR2A was associated with a higher risk of PD(OR=1.137,95％CI:1.058-1.223,P=0.001).Singl e-cell sequencing analyzes protein expression and its dis-tribution among different cell types in the brain.CDNF and CTSB exhibit high expression levels in multiple brain cell types,FCGR2A is predominantly expressed in brain microglia and HBB shows minimal expression in the brain.Conclusion There are potential links between the four proteins CDNF,CTSB,FCGR2A and HBB and the risk of Parkinson's disease.Our results emphasize that the genetic risk variants of Parkinson's disease influence the disease's occurrence by modulating the expression of these immune-related proteins.Additionally,single-cell expression data reveal the expression patterns of these target proteins in the brain.

Pain is a prevalent symptom in both cancer and non-cancer end-stage diseases, often being the most feared by patients and significantly impacting their quality of life.Hospice care aims to address physical, psychological, spiritual, and other needs of patients and their families during this stage, with a focus on alleviating pain and discomfort.Effective pain management is a crucial component of hospice care, particularly given the increasing prevalence of cancer and chronic diseases in China and the growing elderly population.To provide analgesic management for hospice patients, a thorough assessment of pain is essential to identify its type and characteristics.Treatment approaches may include etiological interventions, pharmacotherapy, interventional therapy, physiotherapy, psychotherapy, and comfort care, all aimed at achieving comprehensive pain management.The use of opioid should be carefully guided by scientific principles to minimize adverse effects and optimize pain relief, ultimately enhancing patients' end-of-life quality of life.

Objective:To investigate the correlation between age and tongue pressure in healthy individuals using a newly-developed tongue pressure measuring device.Methods:A total of 154 healthy volunteers aged 20 to 97 years, without noticeable swallowing difficulties, were selected and divided into seven age groups: 20-29 years ( n=24), 30-39 years ( n=22), 40-49 years ( n=20), 50-59 years ( n=24), 60-69 years ( n=22), 70-79 years ( n=22), and 80 years or more ( n=20). Their maximum, minimum, average and initial pressures, work done, and coefficients of variation were measured using the newly designed tongue pressure measuring device in its intermittent and continuous measurement modes. The tongue pressures were correlated with age and gender. Results:The pressure data obtained using the new device were completely consistent with those from a manometer ( R=1). In the intermittent measurement mode, the readings showed that the maximum, minimum and average tongue pressures decreased significantly with age. In the continuous measurement mode, the initial tongue pressure, average pressure and work done also decreased significantly with age, while the coefficient of variation generally increased with age. There was a negative correlation between age and average tongue pressure ( R2=0.4). The relationship could be expressed as y=-0.8595x+ 103.3 (where x is age, and y is tongue pressure). However, no significant correlation was found between gender and tongue pressure. Conclusions:Tongue pressure and its stability are negatively correlated with age in healthy individuals without swallowing dysfunction, showing no significant correlation with gender.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

With the rapid acceleration of aging in China, there is a huge need for elderly patients to have improved quality of life in the terminal stage.Palliative sedation is an integral part of palliative care and can alleviate painful refractory symptoms, and its use in patients in various terminal illnesses is being explored across the world.Attention is focused on its indications and implementation.In China, palliative sedation in clinical practice is in an early exploratory stage and relevant criteria and guidelines have yet to be established.A review of the current practice and research progress concerning palliative sedation for patients' end-of-life care in China and the rest of the world will offer insight and strategic considerations in the initial pursuit and accelerated acceptance in the future in China.

Objective: To determine the efficacy and safety of the Yinmei Kuijie decoction combined with 5-aminosalicylic acid (5-ASA) in treating mildly to moderately active ulcerative colitis (UC) under real-world conditions. Methods: This multicenter, prospective, non-randomized, observational study will be conducted in real-world settings. A total of 204 eligible patients will be consecutively enrolled in the study. Patients in the combination treatment group will receive Yinmei Kuijie decoction in combination with 5-ASA, whereas those in the control group will be treated with 5-ASA alone. The primary endpoint will be a clinical response at week 12, defined as a ≥3 point and ≥30% reduction from baseline in the Mayo total score with ≥1 reduction in rectal bleeding or rectal bleeding score = 0 or 1. Secondary efficacy endpoints at week 12 will include health-related quality of life, mucosal healing, and inflammation indicators. Conclusion The results of this study may provide evidence of the efficacy and safety of Yinmei Kuijie decoction combined with 5-ASA in treating patients with mildly to moderately active UC under real-world principles. The results will provide a basis for further confirmatory studies on the efficacy of Yinmei Kuijie decoction.

Primary sclerosing cholangitis(PSC)is a cholestatic disease characterized by chronic progressive bile duct inflammation and has a low incidence rate and poor prognosis in China.There is still no drug therapy that can change the course of PSC,and liver transplantation is the only effective treatment for PSC,with a 5-year survival rate of 85%after transplantation.Drug therapy for PSC is facing great challenges based on the current status of PSC.At present,drugs for the treatment of PSC are in the stage of clinical trials and have shown certain application prospect,among which ursodeoxycholic acid is the most widely studied and commonly used drug.In addition,there are many emerging drugs in the pipeline.This article summarizes the latest advances in drug therapy for PSC.

Objective:To investigate the prevalence and associated risk of cardiovascular event of resistant hypertension in treated outpatients.Methods:This study was a nationwide multi-center prospective cohort study. The participants were treated outpatients enrolled in the China Nationwide Ambulatory and Home Blood Pressure Registry study of 42 hospitals in 19 provinces across the country from August 2009 to October 2017. Apparent resistant hypertension was defined as uncontrolled office blood pressure (≥140/90 mmHg, 1 mmHg=0.133 kPa) in spite of the use of three antihypertensive drugs or controlled office blood pressure (<140/90 mmHg) with four antihypertensive drugs or more. Subjects diagnosed with uncontrolled office blood pressure were further subdivided as pseudo-resistant hypertension and true resistant hypertension based on 24 h ambulatory blood pressure monitoring. The primary endpoint was fatal and non-fatal cardiovascular and cerebrovascular events, which was a composite endpoint consisting of cardiovascular and cerebrovascular death, ischemic and hemorrhagic stroke, myocardial infarction, coronary artery revascularization, unstable angina, heart failure, and coronary artery stenosis≥50% confirmed by coronary angiography. Secondary outcomes included fatal and non-fatal stroke or cardiac events. Patients with controlled office blood pressure after taking only 1 or 2 antihypertensive drugs were included as control. Kaplan-Meier survival curves, log-rank test, and Cox proportional risk model were used to evaluate the risk of apparent refractory hypertension in relation to cardiovascular and cerebrovascular prognosis.Results:A total of 2 782 treated hypertensive patients, aged (58.1±12.3) years were enrolled, including 1 403 (50.4%) men. The prevalence of apparent and true resistant hypertension was 15.1% (420/2 782) and 10.5% (293/2 782), respectively. Among patients with apparent resistant hypertension, during a median of 5 years follow-up, the cumulative incidence rate was 28.2, 11.2 and 19.1 per 1 000 person-years for fatal and non-fatal cardiovascular events ( n=58), stroke ( n=24) and cardiac events ( n=40), respectively. The Kaplan-Meier curve and log-rank test showed that those patients with true resistant hypertension, had the highest cumulative incidence rate of fatal and non-fatal cardiovascular events, stroke, and cardiac events. Multivariable Cox regression analyses showed that true resistant hypertension was associated with a significantly higher risk of fatal and non-fatal cardiovascular events ( HR=1.73, 95% CI 1.17-2.56, P=0.006) and stroke ( HR=2.81, 95% CI 1.53-5.17, P=0.001). Conclusion:Resistant hypertension, especially true resistant hypertension, is associated with a higher risk of fatal and non-fatal cardiac and cerebrovascular events.