Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Objective:To analyze the influence factors of urinary tract infection after transurethral bipolar plasma enucleation of the prostate (TUPEP) in patients with benign prostatic hyperplasia(BPH), and the early predictive value of serum inflammatory indicators for postoperative urinary tract infection.Methods:A total of 300 patients with BPH who received TUPEP treatment in the Department of Urology, Kailuan General Hospital from January 2021 to August 2023 were selected, according to whether they had urinary tract infections after the operation, they were divided into infection group ( n=117) and non-infection group ( n=183). The clinical data of the two groups were collected, and the serum inflammatory indexes of the two groups were recorded within 24 hours after the operation, including white blood cell count (WBC), neutrophil granulocyte (NE%), high-sensitivity C-reactive protein (hs-CRP), serum amyloid A (SAA), procalcitonin (PCT), heparin-binding protein (HBP), interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and serum ferritin (SF). The differences of clinical data and serum inflammatory indexes between the two groups were analyzed. The measurement data of normal distribution were expressed as mean ± standard deviation ( ± s), and independent sample t-test was used for inter-group comparisons. The measurement data of non- normal distribution were represented by median (interquartile range) [ M ( Q1, Q3)], and the Mann-Whitney U test was used for inter-group comparison. The count data were expressed as cases and percentage, and inter-group comparisons were conducted using the Chi-test. Multivariate Logistic regression analysis was used to explored the influencing factors of urinary tract infections in BPH patients after TUPEP surgery. The receiver operating characteristic (ROC) curve was plotted using GraphPad Prism 8.0.1 medical plotting softwar to evaluate the predictive value of serum inflammatory markers and combined detection of multiple markers for early postoperative urinary tract infections. Results:The duration of disease, history of diabetes, international prostate symptom score (IPSS), prostate volume, preoperative serum prostate-specific antigen (PSA) level, preoperative urine residual volume, operation time, intraoperative blood loss, postoperative catheter indwelling time, and hospitalization time in the infection group were higher than those in the non-infection group ( P<0.05). The preoperative 25-hydroxyvitamin D (25OHD) level and maximum urinary flow rate were lower in the infection group than those in the non- infection group ( P<0.05). Multivariate Logistic regression analysis showed that the course of the disease, history of diabetes, IPSS score, prostate volume, preoperative PSA level, preoperative urine residual volume, operation time, intraoperative blood loss, postoperative catheter indwelling time was positively correlated with urinary tract infection after TUPEP ( B=0.660, 0.242, 0.164, 0.125, 0.230, 0.066, 0.382, 0.022, 0.436, P<0.01), and preoperative 25OHD level and preoperative maximum urinary flow rate were negatively correlated with urinary tract infection after TUPEP ( B=-0.216, -0.372, P<0.01). The levels of hs-CRP, SAA, PCT, HBP, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, SF in the infection group were higher than those in the non-infection group ( P<0.001). The ROC curve analysis showed that the area under the curve (AUC) of hs-CRP, SAA, PCT, HBP, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, SF in early predicting urinary tract infection after TUPEP in BPH patients were 0.697, 0.775, 0.902, 0.873, 0.884, 0.904, 0.917, 0.823, 0.906, 0.852, 0.807, 0.787. The AUC of the combined detection of multiple serum inflammatory markers was 0.972, the sensitivity and specificity were 93.18% and 96.63%, and the sensitivity and specificity of the combined detection of multiple serum inflammatory markers were higher than those of separate detection. Conclusion:The course of BPH, whether to combine history of diabetes, preoperative IPSS score, prostate volume, preoperative PSA level, preoperative 25OHD level, preoperative maximum urinary flow rate, operation time, intraoperative blood loss, and postoperative catheter indwelling time are influencing factors of urinary tract infection after TUPEP, hs-CRP, SAA, PCT, HBP, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-γ, SF had certain value in the early prediction of urinary tract infection after TUPEP in patients with BPH, the combination of multiple indicators can improve the predictive value of early urinary tract infection.

Objective This study explores the clinical correlation between different low-density lipoprotein cholesterol(LDL-C)levels and prognosis,providing evidence-based guidance for the development of personalized lipid-lowering goals.Methods Patients who underwent elective percutaneous coronary intervention(PCI)treatment at Beijing Anzhen Hospital from January 2020 to June 2023 and received lipid-lowering therapy with the addition of Evolocumab were selected.Based on the results of blood lipid rechecks 3 to 6 months after surgery,the patients were divided into five groups:low-density lipoprotein＜0.5 mmol/L,0.5 to＜1.0 mmol/L,1.0 to＜1.4 mmol/L,1.4 to＜1.8 mmol/L,and above 1.8 mmol/L.All patients were followed up for more than one year,and clinical conditions and major adverse cardiovascular events(MACE)were recorded.Results A total of 1 106 patients undergoing PCI were enrolled;after propensity score matching and exclusion of patients lost to follow up,550 remained(110 per group).During 12 months of follow-up,58 patients(10.5％)experienced a MACE,with incidence rising step-wise across LDL-C categories.In multivariable Cox models adjusted for age,sex,diabetes,hypertension,baseline LDL-C,follow-up LDL-C,estimated glomerular filtration rate(eGFR),and left ventricular ejection fraction,the hazard ratios[HR(95％CI)]for MACE,relative to the＜0.5 mmol/L group,were 1.810(0.507-6.454,P=0.361),3.036(0.945-9.749,P=0.062),5.228(1.737-15.735,P=0.003),7.708(2.633-22.565,P＜0.001)for LDL-C levels of 0.5 to＜1.0,1.0 to＜1.4,1.4 to＜1.8 and≥ 1.8 mmol/L,respectively.A restricted cubic spline model demonstrated a significant non-linear positive association between LDL-C and MACE(P-overall≤0.001;P-non-linear=0.008).Stratified analyses by age,sex,hypertension and diabetes showed consistent HR with no significant interactions(all P＞0.05).There were no statistically significant differences among the groups in the incidence of bleeding events,elevated creatinine levels,or abnormal liver function(all P＞0.05).Conclusions In patients using PCSK9 after PCI,there is a significant positive correlation between LDL-C levels and the risk of MACE,and no correlation was observed between different LDL-C levels and the risk of adverse events such as bleeding.

The medical ultrasonic nebulizer was introduced in terms of composition,working principle and testing principle and method of the maximum nebulization rate.The testing characteristics of the volumetric and gravimetric methods were compared.A series of experiments were conducted using the whole-unit gravimetric approach.The initial liquid charge was indicated to be the primary factor affecting the maximum nebulization rate,and the influence increased significantly when the nebulizer's nominal volume got expanded.References were provided for medical testing staffs in selecting testing methods.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:This study aimed to investigate the regulatory role and mechanism of myosin heavy chain 9 (MYH9) in the invasion of Zika virus (ZIKV) into human glioma cells (U251).Methods:Utilizing CRISPR/Cas9 technology, MYH9-knockout U251 cells (U251-MYH9 KD) were constructed. Following ZIKV infection, the protein expression levels, RNA load, and viral titer of ZIKV were detected through western blot (WB), Real-time fluorescence quantitative polymerase chain reaction (qPCR), and plaque formation assays, respectively. The infection efficiency of ZIKV in U251 cells treated with the MYH9 inhibitor blebbistatin was assessed. The binding and internalization efficiency of ZIKV were measured in U251-MYH9 KD cells. The interaction between MYH9 and the ZIKV envelope protein (E) was studied using co-immunoprecipitation (Co-IP). The effects of soluble MYH9 recombinant protein and anti-human MYH9 antibodies on ZIKV infection were evaluated by qPCR and plaque formation assays. Results:It was found that knockout or inhibition of MYH9 significantly suppressed ZIKV infection in U251 cells. MYH9 knockout notably inhibited the binding and internalization of ZIKV in U251 cells. MYH9 interacted with the ZIKV E protein, and both MYH9 recombinant protein and anti-human MYH9 antibodies, by blocking the binding of ZIKV E protein to cell surface MYH9, inhibited ZIKV infection in U251 cells in a dose-dependent manner.Conclusions:MYH9 facilitates ZIKV invasion into U251 cells through interaction with the ZIKV E protein.

The medical ultrasonic nebulizer was introduced in terms of composition,working principle and testing principle and method of the maximum nebulization rate.The testing characteristics of the volumetric and gravimetric methods were compared.A series of experiments were conducted using the whole-unit gravimetric approach.The initial liquid charge was indicated to be the primary factor affecting the maximum nebulization rate,and the influence increased significantly when the nebulizer's nominal volume got expanded.References were provided for medical testing staffs in selecting testing methods.

To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.

OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology