ObjectiveThis study aimed to investigate whether Bushen Tongluo prescription inhibits macrophage polarization by regulating the Wnt3a/β-catenin signaling pathway， thereby reducing epithelial-mesenchymal transition and excessive extracellular matrix deposition， in order to elucidate the anti-pulmonary fibrosis mechanisms of Bushen Tongluo prescription and provide a new theoretical basis for the clinical treatment of pulmonary fibrosis. MethodsFifty male Sprague-Dawley （SD） rats were randomly divided into a blank group， model group， pirfenidone group， and high- and low-dose Bushen Tongluo prescription groups. Except for the blank group， the pulmonary fibrosis model was established by intratracheal instillation of bleomycin. Intervention was initiated on day 28 after modeling. The high- and low-dose Bushen Tongluo prescription groups were administered Bushen Tongluo prescription at doses of 30.88， 15.44 g·kg^-1， respectively， by intragastric gavage. The pirfenidone group was administered pirfenidone capsules at 110 mg·kg^-1 by intragastric gavage. The blank and model groups were given an equal volume of normal saline by gavage， once daily for 90 days. After treatment， the level of transforming growth factor-β₁ （TGF-β₁） in bronchoalveolar lavage fluid （BALF） was detected by enzyme-linked immunosorbent assay （ELISA）. Morphological changes in lung tissue and the collagen volume fraction were compared. The protein distribution and expression of E-cadherin， cytokeratin 19， α-smooth muscle actin （α-SMA）， vimentin， collagen type Ⅰ （Col Ⅰ）， and collagen type Ⅲ （Col Ⅲ） in lung tissue were detected by immunohistochemistry. The protein distribution and expression of CD68， arginase-1 （Arg-1）， inducible nitric oxide synthase （iNOS）， Wnt3a， and β-catenin in lung tissue were detected by immunofluorescence. The protein expression of Wnt3a and β-catenin in lung tissue was detected by Western blot， and the mRNA expression of Wnt3a and β-catenin was detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， a large number of inflammatory cells infiltrated the airway walls， alveolar spaces， and interstitial tissue in the model group， with obvious fibrous tissue hyperplasia. The level of TGF-β₁ in BALF was significantly increased. The protein expression of E-cadherin and cytokeratin 19 in lung tissue was decreased， whereas the protein expression of α-SMA， Vimentin， Wnt3a， β-catenin， Col Ⅰ， and Col Ⅲ was increased. The fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue were increased. The protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue were significantly increased （P<0.01）. Compared with the model group， all treatment groups showed varying degrees of improvement in inflammatory cell infiltration and fibrous tissue hyperplasia in the airway walls， alveolar spaces， and interstitial tissue， decreased TGF-β₁ levels in BALF， increased protein expression of E-cadherin and cytokeratin 19 in lung tissue， decreased protein expression of α-SMA， Vimentin， Col Ⅰ， and Col Ⅲ， decreased fluorescence-positive area ratios of CD68， Arg-1， iNOS， Wnt3a， and β-catenin in lung tissue， and decreased protein and mRNA expression levels of Wnt3a and β-catenin in lung tissue （P<0.05， P<0.01）. ConclusionBushen Tongluo prescription can improve bleomycin-induced pulmonary fibrosis in rats by inhibiting epithelial-mesenchymal transition and reducing excessive extracellular matrix deposition. The mechanism may be related to inhibition of the Wnt3a/β-catenin signaling pathway and the macrophage polarization mediated by this pathway.

OBJECTIVES: To investigate the effects of different filtration fractions (FFs) during continuous venovenous hemodiafiltration (CVVHDF) post-dilution. METHODS: This study employed a single-blind, head-to-head randomized controlled design. Patients who underwent daytime continuous renal replacement therapy (CRRT) in the Department of Nephrology, the Second Affiliated Hospital of Nanchang University between April 2022 and June 2023 were prospectively enrolled. They were randomly assigned to either a low FF group (FF set at 20%-<25%) or a high FF group (FF set at 25%-30%). All patients received post-dilution CVVHDF with systemic heparin anticoagulation. The primary outcome was extracorporeal circuit coagulation, comprehensively assessed through dynamic monitoring of arterial pressure, venous pressure, and transmembrane pressure, combined with filter clotting grading at the end of the session. Secondary outcomes included changes in serum creatinine, urea, potassium, and pH levels before and after treatment to evaluate efficacy. RESULTS: A total of 40 patients were included in each the low FF group and the high FF group. The baseline characteristics showed no statistically significant differences between the two groups (all P>0.05). All patients completed the treatment successfully, with a treatment duration of 10-12 hours, and no filter required replacement during the sessions. The differences in arterial pressure, venous pressure, and transmembrane pressure at 2 h, 6 h, and the end of treatment compared to values at 1 h showed no statistically significant differences between the two groups (all P>0.05). Furthermore, no significant difference was found in filter clotting grades (including Grade Ⅰ and Grade Ⅱ clotting) at the end of treatment between the two groups (all P>0.05). The creatinine clearance efficiency was significantly higher in the high FF group compared to the low FF group (P<0.01). However, no statistically significant differences were observed between the groups regarding urea reduction, or the changes in serum potassium and pH levels before and after treatment (all P>0.05). CONCLUSIONS For patients with a relatively short treatment duration of 10-12 h undergoing post-dilution CVVHDF, employing a FF of 25%-30% does not pose a higher risk of extracorporeal circuit coagulation compared to a FF of 20%-25%, but shows a trend towards higher creatinine clearance.

Interferon regulatory factor 4 (IRF4) is a critical transcription factor that governs the differentiation of cluster of differentiation 4⁺ (CD4⁺) T cells. The pathogenesis and progression of psoriasis are primarily attributed to an immune imbalance stemming from the overproduction of interleukin-17A (IL-17A) by T lymphocytes. However, the role of IRF4 in psoriasis remains unexplored. In this study, we found that IRF4 activity is increased in the cutaneous lesions of patients with psoriasis in response to stimulation by IL-23A and IL-1β. This IRF4 elevation heightens its binding to the E1A binding protein p300 (EP300) promoter, triggering the transcription of downstream retinoic acid receptor-related orphan receptor-γt (RORγt) and increasing the secretion of IL-17A, thereby establishing the IL-1β/IL-23A-IRF4-EP300-RORC-IL-17A inflammatory cascade in psoriasis. The alleviation of imiquimod (IMQ)-induced psoriatic-like symptoms was achieved through the creation of a Irf4 ^-/- gene deletion mouse model and pharmacological inhibition using antisense oligonucleotides targeted for Irf4. This amelioration was accompanied by a decreased number of IL-17A-producing CD4⁺ T cells in the skin. The findings of this study suggest that IRF4 plays a crucial role in the promotion of inflammation and exacerbation of IMQ-induced psoriasiform dermatitis. Consequently, IRF4 targeting could be a promising therapeutic strategy.

OBJECTIVE: To explore the risk factors affecting the prognosis of patients with sepsis complicated with acute pulmonary embolism, and to construct and validate a nomogram predictive model for in-hospital mortality risk. METHODS: Based on the American Medical Information Mart for Intensive Care (MIMIC-III, MIMIC-IV) databases, the data were collected on patients with sepsis complicated with acute pulmonary embolism from 2001 to 2019, including baseline characteristics, and vital signs, disease scores, laboratory tests within 24 hours of admission to the intensive care unit (ICU), and interventions. In-hospital mortality was the outcome event. The total samples were divided into training and testing sets in a 7:3 ratio by random sampling. Univariate Cox regression analysis was used to verify the impact of all variables on the risk of in-hospital mortality, thereby screen potential influencing factors. Subsequently, a stepwise bi-directional regression method was applied to select factors one by one, leading to the construction of a nomogram prediction model. Collinearity testing was used to demonstrate the absence of strong multicollinearity among the influencing factors in the nomogram prediction model. The discrimination of the nomogram model, sequential organ failure assessment (SOFA), and simplified pulmonary embolism severity index (sPESI) was evaluated using C-index in the test set. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of various models for in-hospital mortality in patients with sepsis complicated with acute pulmonary embolism. RESULTS: A total of 562 patients with sepsis complicated with acute pulmonary embolism were included, including 393 in the training set and 169 in the testing set. Univariate Cox regression analysis showed that 30 factors associated with in-hospital mortality in patients with sepsis complicated with acute pulmonary embolism. Through stepwise bi-directional regression, 12 variables were ultimately selected, including gender, presence of malignant tumors, body temperature, red cell distribution width (RDW), blood urea nitrogen (BUN), serum potassium, prothrombin time (PT), 24-hour urine output, mechanical ventilation, vasoactive drugs, warfarin use, and sepsis-induced coagulopathy (SIC). Collinearity testing indicated no strong multicollinearity among the influencing factors [all variance inflation factor (VIF) > 10]. A nomogram model was constructed using the 12 variables mentioned above. The nomogram model predicted the C-index and its 95% confidence interval (95%CI) of in-hospital mortality in patients with sepsis complicated with acute pulmonary embolism better than SOFA score and sPESI [0.771 (0.725-0.816) vs. 0.579 (0.519-0.639), 0.608 (0.554-0.663)]. The ROC curve showed that the area under the curve (AUC) and its 95%CI of the nomogram model were higher than those of the SOFA score and sPESI [0.811 (0.766-0.857) vs. 0.630 (0.568-0.691), 0.623 (0.566-0.680)]. These findings were consistently replicated in the internal validation of the testing set. In both the training and testing sets, Delong's test showed that the AUC of the nomogram model was significantly higher than the SOFA score and sPESI (both P < 0.05). CONCLUSION The nomogram model demonstrated good predictive effectiveness for the risk of in-hospital mortality in patients with sepsis complicated with acute pulmonary embolism, enabling clinicians to predict mortality risk in advance and take timely interventions to reduce mortality.
Humans ; Pulmonary Embolism/mortality* ; Hospital Mortality ; Nomograms ; Sepsis/complications* ; Prognosis ; Risk Factors ; Intensive Care Units ; Male ; Female ; Middle Aged ; Aged

[Objective] To establish a cryopreservation protocol for small-volume (≤1 mL) red blood cells (RBCs) and to evaluate the reactivity and stability of blood group antigens after cryopreservation, so as to explore its potential application in immunohematology reference laboratories. [Methods] Small-volume RBCs were cryopreserved for 120 days, followed by thawing and deglycerolization to restore the RBC components. The quality of the RBCs was assessed. Serum antibodies were serially diluted and reacted with RBCs before and after cryopreservation, and agglutination scores were recorded to quantitatively evaluate the reactivity and stability of blood group antigens such as Rh, Duffy, Lewis, Kidd, M, and H. Flow cytometry was used to analyze the percentage and mean fluorescence intensity of ABO antigen expression on RBCs before and after cryopreservation to assess the usability of cryopreserved RBCs in flow immunophenotyping and blood group subtype studies. [Results] The hemolysis rate of thawed and deglycerolized RBCs was (0.27±0.10)%, with a supernatant free hemoglobin level of (0.52±0.14) g/L, and the RBC recovery rate was (69.12±7.91)%. The direct antiglobulin test (DAT) was negative for all thawed RBCs. There was no difference in the reactivity of blood group antigens before and after cryopreservation, and no difference in the percentage and mean fluorescence intensity of A and B antigen expression on RBCs before and after cryopreservation. [Conclusion] The small-volume RBC cryopreservation protocol can be applied to immunohematology analysis in reference laboratories and is expected to be widely used in blood group identification, antibody screening, identification, and blood group-related research.

Objective:To assess the current status of geriatrics department development in public general hospitals at or above the second grade in Shandong province.Methods:A cross-sectional survey was conducted from October 27 to November 3, 2023 using a web-based electronic questionnaire to investigate the current status of geriatrics department development in all public general hospitals at or above the second grade across 16 prefecture-level cities in Shandong province.The survey included participation from medical department staff and managers of geriatric medicine departments.Results:Shandong province has 355 public general hospitals at or above the second grade, of which 337 completed the questionnaire.Among these 337 hospitals, 92.28%(311/337)have established geriatric departments, 83.09%(280/337)have set up geriatric clinics, 69.14%(233/337)have independent geriatric wards, and 71.51%(241/337)have implemented comprehensive geriatric assessments(CGA).Regarding the configuration of geriatric departments, 60.24%(203/337)of hospitals met the requirement of having at least 20 ward beds, 34.42%(116/337)met the doctor-to-bed ratio requirement of at least 0.3, and 22.26%(75/337)met the nurse-to-bed ratio requirement of at least 0.6.Only 13 hospitals met all the requirements for geriatric wards, beds, doctors, and nurses, accounting for 3.86%(13/337)of the participating hospitals.Conclusions:The establishment of geriatrics departments in second-grade or higher public general hospitals in Shandong province has surpassed the national target in China ahead of schedule.Most hospitals have established geriatric clinics and wards and have implemented CGA.However, significant challenges remain, including a shortage of ward beds and a lack of medical staff.

Objective:To investigate the clinicopathological characteristics, molecular features, differential diagnosis and prognosis of renal cell carcinoma (RCC) with TFEB gene amplification.Methods:A total of 113 cases of unclassified RCCs and RCCs with TFEB positive expression were collected from the Affiliated Hospital of Qingdao University and Navy 971 Hospital from January 2010 to December 2024. Eight cases of RCCs with TFEB amplification were identified using tissue microarrays, immunohistochemistry, and fluorescence in situ hybridization (FISH) techniques. The clinicopathological data and prognosis of the 8 cases were summarized, and relevant literature was reviewed.Results:Among the 8 cases, there were 5 males and 3 females. The average age was 63.4 (54, 77) year and the median age was 63.5 (59.0, 65.5) year. Seven cases were detected through physical examination, and 1 case presented with initial symptoms of metastasis to bones and lungs. The cohort included 1 biopsy specimen and 7 surgical resection specimens. The tumor diameters ranged from 2.5 to 15.0 cm. The cut surfaces of 5 cases were grayish-yellow or grayish-red, and 2 cases exhibited a colorful appearance, among which 3 cases involved renal sinus and 1 case showed invasion of the perirenal fat tissue. Microscopically, 4 cases were composed of clear cells arranged in solid sheets or acinar structures, along with varying numbers of eosinophilic cells. Two cases exhibited the morphology of high-grade eosinophilic RCC, and 1 case presented biphasic morphology with diffuse polygonal eosinophilic tumor cells and dense small cell components. The remaining 1 case exhibited the morphology of clear cell RCC. According to the WHO/ISUP nuclear grading system, 6 cases were Grade 3 and 2 cases were Grade 2. Multifocal necrosis was observed in 4 cases. In 4 surgical specimens, the tumor tissue invaded the renal parenchyma, with 2 cases showing nodular infiltration to surrounding tissues and 1 case with intravascular tumor thrombus. Immunohistochemical results showed varying degrees of TFEB nuclear positivity in 6 cases (6/8). Melanocytic markers such as Melan A (5/8) and HMB45 (3/8) were expressed at varying degrees. Cathepsin K (6/8), GPNMB (6/8), P504s (7/8) and CD10 (7/8) were positively expressed in most cases. FISH results revealed high-copy amplification of TFEB gene in 4 cases (partially showing clustered amplification) and low-copy amplification in 4 cases. During the follow-up period of 3 to 64 months of the 8 cases, 3 cases metastasized and 2 cases died of disease (both with high-copy TFEB gene amplification).Conclusions:RCC with TFEB gene amplification is rare and exhibits diverse morphological features. A common morphological characteristic of this type of tumor is a mixture of sheet-like clear cells and high nuclear grade eosinophilic cells. Combined immunohistochemical staining for TFEB, melanocytic markers, and GPNMB is helpful for the diagnosis of the tumor, and FISH detection of TFEB gene amplification is the most definitive method in diagnosing this tumor. RCC with TFEB gene amplification usually presents with strong aggressiveness and poor prognosis. Combining surgical resection with immunotherapy or VEGFR-targeted drugs might have therapeutic effects on the tumor.

With the change of infectious disease incidence pattern and the development of related technologies, progresses have been made in the research of infectious disease epidemiology. In recent years, due to the change in the requirements of infectious disease prevention and control, the research focus has expanded from common infectious diseases to diseases which have been eliminated or might be eliminated, as well as emerging and re-emerging infectious diseases. Infectious disease data has been characterized by multiple sources and modalities. Along with the rapid development of pathogen detection methods, infectious disease surveillance has shifted from a single disease-targted one to a comprehensive one. Moreover, novel technologies such as multi-omics and artificial intelligence have been applied in infectious disease epidemiology research. The international cooperation in this field has become increasingly crucial, and the revision of the International Health Regulations and the negotiation of pandemic agreement will have a profound impact. In the future, infectious disease epidemiology research will develop with more powerful tools to improve its capabilities.