BACKGROUND: Chronic kidney disease (CKD) poses a major global health challenge, often foreshadowing poor patient outcomes. The C-reactive protein to albumin ratio (CAR) serves as a pivotal biomarker, demonstrating a strong correlation with adverse outcomes in cardiovascular disease (CVD). This study sought to examine the correlation between CAR and the risk of all-cause and cardiovascular mortality in patients with CKD stages 3-5. METHODS: This study utilized data of CKD patients from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010, with follow-up to December 31, 2019. The optimal CAR cutoff value was identified utilizing the method of maximally selected rank statistics. Multivariable Cox proportional hazards regression model, restricted cubic splines (RCS) model, and subgroup analysis were employed to assess the association between CAR and mortality among CKD patients. RESULTS: During a median (with interquartile range) follow-up period of 115 (112,117) months among 2,841 CKD individuals, 1,893 deaths were observed, including 692 deaths due to CVD events. Based on the RCS analysis, a non-linear correlation was observed between CAR and mortality. Using 0.3 as the optimal CAR cutoff value, the cohort was divided into high and low groups. In the fully adjusted model, CKD patients with high CAR values exhibited an elevated risk of all-cause mortality (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.28-1.83, P < 0.001) and cardiovascular mortality (HR 1.48, 95% CI 1.08-2.02, P = 0.014). Compared to the population aged >65 years (HR 1.32, 95% CI 0.99-1.76, P = 0.064), the risk of cardiovascular mortality was significantly higher in those aged ≤65 years (HR 2.19, 95% CI 1.18-4.09, P = 0.014) with elevated CAR levels. CONCLUSIONS A notable correlation exists between the elevation of CAR and increased all-cause and cardiovascular mortality, suggesting its potential as an independent indicator for evaluating the prognosis of patients with CKD stages 3-5.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Cardiovascular Diseases/blood* ; Male ; Female ; Middle Aged ; C-Reactive Protein/metabolism* ; Aged ; Biomarkers/blood* ; Nutrition Surveys ; Adult ; United States/epidemiology* ; Serum Albumin/analysis*

Macrophages derived from the human THP-1 cell line have been widely used as substitutes for primary macrophages in various macrophage-related studies. However, difficulties still exist in establishing THP-1 macrophage models. This research presents techniques for generating different phenotypes of activated macrophages derived from THP-1 cells by introducing specific stimuli and provides some potential markers to confirm each type of activated macrophage. It is hoped to provide novel and useful methods for scientific research and to help researchers explore this field more intuitively and effectively.
Humans ; Macrophages/physiology* ; THP-1 Cells ; Cell Culture Techniques/methods* ; Macrophage Activation ; Cell Polarity ; Cell Differentiation ; Phenotype ; Cell Line

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

OBJECTIVE: To assess the relationship between blood pressure reactivity index (BPRI) and in-hospital mortality risk in patients with sepsis-associated acute kidney injury (SA-AKI). METHODS: A retrospective cohort study was conducted to collect data from patients admitted to the intensive care unit (ICU) and clinically diagnosed with SA-AKI between 2008 and 2019 in the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database in the United States. The collected data included demographic characteristics, comorbidities, vital signs, laboratory parameters, sequential organ failure assessment (SOFA) and simplified acute physiology scoreII(SAPSII) within 48 hours of SA-AKI diagnosis, stages of AKI, treatment regimens, mean BPRI during the first and second 24 hours (BPRI_0_24, BPRI_24_48), and outcome measures including primary outcome (in-hospital mortality) and secondary outcomes (ICU length of stay and total hospital length of stay). Variables with statistical significance in univariate analysis were included in LASSO regression analysis for variable selection, and the selected variables were subsequently incorporated into multivariate Logistic regression analysis to identify independent predictors associated with in-hospital mortality in SA-AKI patients. Restricted cubic spline (RCS) analysis was employed to examine whether there was a linear relationship between BPRI within 48 hours and in-hospital mortality in SA-AKI patients. Basic prediction models were constructed based on the independent predictors identified through multivariate Logistic regression analysis, and receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive performance of each basic prediction model before and after incorporating BPRI. RESULTS: A total of 3 517 SA-AKI patients admitted to the ICU were included, of whom 826 died during hospitalization and 2 691 survived. The BPRI values within 48 hours of SA-AKI diagnosis were significantly lower in the death group compared with the survival group [BPRI_0_24: 4.53 (1.81, 8.11) vs. 17.39 (5.16, 52.43); BPRI_24_48: 4.76 (2.42, 12.44) vs. 32.23 (8.85, 85.52), all P < 0.05]. LASSO regression analysis identified 20 variables with non-zero coefficients that were included in the multivariate Logistic regression analysis. The results showed that respiratory rate, temperature, pulse oxygen saturation (SpO₂), white blood cell count (WBC), hematocrit (HCT), activated partial thromboplastin time (APTT), lactate, oxygenation index, SOFA score, fluid balance (FB), BPRI_0_24, and BPRI_24_48 were all independent predictors for in-hospital mortality in SA-AKI patients (all P < 0.05). RCS analysis revealed that both BPRI showed "L"-shaped non-linear relationships with the risk of in-hospital mortality in SA-AKI patients. When BPRI_0_24 ≤ 14.47 or BPRI_24_48 ≤ 24.21, the risk of in-hospital mortality in SA-AKI increased as BPRI values decreased. Three basic prediction models were constructed based on the identified independent predictors: Model 1 (physiological indicator model) included respiratory rate, temperature, SpO₂, and oxygenation index; Model 2 (laboratory indicator model) included WBC, HCT, APTT, and lactate; Model 3 (scoring indicator model) included SOFA score and FB. ROC curve analysis showed that the predictive performance of the basic models ranked from high to low as follows: Model 3, Model 2, and Model 1, with area under the curve (AUC) values of 0.755, 0.661, and 0.655, respectively. The incorporation of BPRI indicators resulted in significant improvement in the discriminative ability of each model (all P < 0.05), with AUC values increasing to 0.832 for Model 3+BPRI, 0.805 for Model 2+BPRI, and 0.808 for Model 1+BPRI. CONCLUSIONS BPRI is an independent predictor factor for in-hospital mortality in SA-AKI patients. Incorporating BPRI into the prediction model for in-hospital mortality risk in SA-AKI can significantly improve its predictive capability.
Humans ; Acute Kidney Injury/mortality* ; Sepsis/complications* ; Retrospective Studies ; Hospital Mortality ; Prognosis ; Blood Pressure ; Intensive Care Units ; Male ; Female ; Length of Stay ; Middle Aged ; Aged ; Adult ; Logistic Models

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.
Mice ; Animals ; Hypoxia ; Oxidative Stress ; Autophagy ; Cognition ; Sirolimus/therapeutic use*

【Objective】 To explore the factors influencing erectile dysfunction (ED) in male patients after renal transplantation, so as to provide basis for the prevention and treatment of this disease. 【Methods】 Kidney transplant recipients followed up in the Kidney Transplant Clinic of Xijing Hospital during Sep.1, 2022 and May 1, 2023 were selected as the study objects.Questionnaires were distributed, and the erectile function was measured with Sexual Health Inventory for Men (SHIM).Factors associated with ED were analyzed with multivariate logistic regression. 【Results】 A total of 300 questionnaires were distributed, and 276 valid ones were collected, including 182 cases (65.9%) suffering from ED of varying degrees.Multivariate logistic regression analysis showed that age [(<30 years/>50 years, OR: 0.120, 95%CI: 0.033-0.405, P<0.001), (30-40 years/>50 years, OR: 0.223, 95%CI: 0.102-0.463, P<0.001), (>40-50 years/>50 years, OR: 0.320, 95%CI: 0.139-0.719, P<0.01)], level of International Prostate Symptom Score (IPSS) (OR: 1.95, 95%CI: 1.211-3.248, P<0.01), International Prostate Symptom Score-Quality of Life item (IPSS-QoL) (OR: 1.482, 95%CI: 1.201-1.854, P<0.01), and income [(≥10 000 Yuan/<3 000 Yuan, OR: 0.156, 95%CI: 0.053-0.429, P<0.001), (5 000-<10 000 Yuan/<3 000 Yuan, OR: 0.418, 95%CI: 0.199-0.864, P<0.05), (≥10 000 Yuan/3 000-<5 000 Yuan, OR: 0.205, 95%CI: 0.069-0.573, P<0.01)] were independent and significant factors of ED. 【Conclusion】 The prevalence of ED in renal transplantation recipients is high.Age, income, IPSS and IPSS-QoL are the influencing factors.ED after renal transplantation is not only determined by physical and functional factors, but also closely related to social and psychological factors.

Brachial plexus avulsion (BPA) is a combined injury involving the central and peripheral nervous systems. Patients with BPA often experience severe neuropathic pain (NP) in the affected limb. NP is insensitive to the existing treatments, which makes it a challenge to researchers and clinicians. Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction, which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP. However, the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear. In this study, through using a novel BPA C7 root avulsion mouse model, we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased, and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors (α1-AR and α2-AR) also increased after BPA. The phenomenon of superexcitation of the sympathetic nervous system, including hypothermia and edema of the affected extremity, was also observed in BPA mice by using CatWalk gait analysis, an infrared thermometer, and an edema evaluation. Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice. Further, intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice. In another branch experiment, we also found the elevated expression of BDNF, TrκB, TH, α1-AR, and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry. Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP. This study also opens a novel analgesic target (BDNF) in the treatment of this pain with fewer complications, which has great potential for clinical transformation.
Humans ; Mice ; Animals ; Hyperalgesia/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Hypothermia/metabolism* ; Neuralgia ; Brachial Plexus/injuries* ; Edema/metabolism*

【Objective】 To analyze the correlation between the expressions of CD10,CA9 and CD133 and the prognosis of patients with metastatic renal clear cell carcinoma (mccRCC) treated with sorafenib or sunitinib. 【Methods】 A total of 80 mccRCC patients who received sorafenib or sunitinib as first-line therapy were retrospectively enrolled. Immunohistochemical staining (IHC) was performed for CD10,CA9 and CD133 in tumor tissue samples to analyze the correlation between the expression of each marker and clinicopathologic variables. Univariate and multivariate Cox proportional risk models were used to analyze prognostic factors of progression free survival (PFS) and overall survival (OS),and Kaplan-Meier survival analysis was performed for CA9 expression and PFS,OS in the treatment subgroups. 【Results】 Altogether 37 patients (46.25%) had PFS,and the median PFS (mPFS) was 24.9 months (95%CI:16.5-33.2 months),while 55 patients (68.75%) died and the median OS (mOS) was 44.2 months (95%CI:14.6-73.7). Low expression of CD10 was correlated with high Fuhrman grade (χ²=6.241,P=0.012),lymph node metastasis (χ²=5.952,P=0.015),and the number of metastatic organs ≥2 (χ²=8.205,P=0.004). Univariate analysis showed that Fuhrman grade,number of metastatic organs and lymph node metastasis were the prognostic factors of PFS (P<0.05),while the number of metastatic organs,lymph node metastasis and CA9 expression were the prognostic factors of OS (P<0.05). Multivariate analysis showed that Fuhrman grade was an independent factor of PFS (HR=2.457,95%CI:1.126-5.365,P=0.024),and the number of metastatic organs was an independent prognostic factor of OS (HR=1.857,95%CI:1.048-3.290,P=0.034). Survival analysis in subgroups showed that high CA9 expression in the sorafenib group was associated with longer OS (HR=0.401,95%CI:0.204-0.787,P=0.008). 【Conclusion】 Low expression of CA9 is an non-independent risk factor for OS,while CD10 and CD133 cannot be used as prognostic factors for mccRCC patients. Since mccRCC patients with low CA9 expression have less survival benefit from sorafenib and sunitinib,they can choose target therapy combined with immunotherapy or dual immunotherapy according to the guidelines to improve prognosis.

Premature ejaculation (PE) is the most common male sexual dysfunction with a high incidence, which seriously affects the relationship between a husband and wife and family harmony. Drug therapy is a first-line treatment for PE patients with premature ejaculation, and has achieved good efficacy, but the clinically available drugs are single and the abandonment rate is high. Coupled with the ineffective treatment of some patients, new drug research and development is imminent. This paper systematically reviews the current status of drug treatment for premature ejaculation, focusing on the research and development of new drugs and research progress in order to provide a reference for clinicians.

Malignant mesothelioma of the tunica vaginalis testis (MMTVT) is a rare tumor. At present, there are still many disputes in its epidemiology, pathogenesis, selection of diagnostic methods, treatment and prognosis. Asbestos exposure, ionizing radiation and chromosome abnormalities are the risk factors of MMTVT. Immunohistochemistry, ultrasonography and electron microscope can be used for the diagnosis and aggressive surgery is the main treatment method. The development of endoscopic surgery, multi-disciplinary treatment (MDT), tumor targeted therapy and immunotherapy will bring more benefits to MMTVT patients.