Objective: To analyze the changing trend and distribution characteristics of hepatitis C virus (HCV) infection among blood donors in Hebei, thereby providing data to support strategy and procedure adjustment for blood collection and supply institutions. Methods: Data from 12 blood stations in Hebei Province from 2012 to 2021 were collected. These data were analyzed to determine trends in anti-HCV antibody double reagent reactive rate and to characterize its distribution among different donor categories, genders and birth cohorts. Results: During the period from 2012 to 2021, a total of 7.4576 million samples were tested at 12 blood stations in Hebei Province, with 3.4659 million (46.47%) from first-time donors, and 3.9917 million (53.53%) from repeat donors. The number (of anti-HCV double reagent reactive samples was 7167 (9.61/10 000). The anti-HCV double reagent reactive rate showed a annual downward trend (P<0.05), from 17.40/10 000 at the beginning to 4.95/10 000 at the end of the study period. Additionally, the double reagent reactive rate of repeat blood donors had remained below 1/10 000 since 2017. The double reagent reactive rate of first-time blood donors (19.42/10 000) was higher than in repeat donors (1.09/10 000) (P<0.05), and the double-reagent reactive rate of female first-time blood donors (20.98/10 000) was higher than that of male first-time blood donors (18.49/10 000) (P<0.05). The anti-HCV double reagent reactive rate among first-time donors exhibited two distinct peaks within the pre-1976 and 1989-1994 birth cohorts, with notable gender differences observed in both peak periods. The rate of double reagent reactive in females born before 1976 (52.22/10 000) was higher than that in males (32.28/10 000) (P<0.05), while that of males born in 1989-1994 was higher (25.75/10 000) than that of females (14.28/10 000) (P<0.05). Conclusion: The prevalenc of HCV infection among blood donors in Hebei Province has shown a consistent year-over-year decline over the study period. The majority of infected individuals are found among the first-time blood donors born before 1995. These trends and characteristics provide valuable insights for developing pre-blood collection screening strategies, analyzing nucleic acid test data in blood screening, adjusting blood screening procedures, and provide evidence for targeted screening of high-risk populations as part of public health initiatives to eliminate hepatitis C.

As an important strategy in antiviral drug development, nucleoside analogs (NAs) have attracted considerable attention due to their unique mechanisms of action and favorable safety profile. This review systematically summarizes recent advances in the mechanisms of action of NAs, focusing on the following four aspects: (1) Targeting viral polymerases, inhibiting viral replication through mechanisms such as non-absolute termination, delayed chain termination and induction of viral RNA mutations in addition to classical chain termination, which has been newly discovered; (2) Regulating RNA methylation modifications—for instance, competitively inhibiting methyltransferases, which significantly reduces viral replication efficiency; (3) Depleting nucleotide pools—by affecting host cell purine nucleotide synthesis pathways, thereby indirectly inhibiting viral replication; and (4) Immunomodulatory functions—including activation of the STING pathway to promote interferon production. Furthermore, this review systematically discusses the breakthrough progress in prodrug technologies for addressing key clinical challenges such as drug resistance and off-target toxicity of NAs. These advances provide crucial technical support for the clinical translation of NAs. These advances provide key technical support for the clinical translation of NAs. This review clarifies the multi-target action rules of NAs and provides a theoretical framework for the design of next-generation broad-spectrum antiviral agents.

OBJECTIVES: Osteoarthritis (OA) and sarcopenia are significant health concerns in the elderly, substantially impacting their daily activities and quality of life. However, the relationship between them remains poorly understood. This study aims to uncover common biomarkers and pathways associated with both OA and sarcopenia. METHODS: Gene expression profiles related to OA and sarcopenia were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between disease and control groups were identified using R software. Common DEGs were extracted via Venn diagram analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to identify biological processes and pathways associated with shared DEGs. Protein-protein interaction (PPI) networks were constructed, and candidate hub genes were ranked using the maximal clique centrality (MCC) algorithm. Further validation of hub gene expression was performed using 2 independent datasets. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of key genes for OA and sarcopenia. Mouse models of OA and sarcopenia were established. Hematoxylin-eosin and Safranin O/Fast Green staining were used to validate the OA model. The sarcopenia model was validated via rotarod testing and quadriceps muscle mass measurement. Real-time reverse transcription PCR (real-time RT-PCR) was employed to assess the mRNA expression levels of candidate key genes in both models. Gene set enrichment analysis (GSEA) was conducted to identify pathways associated with the selected shared key genes in both diseases. RESULTS: A total of 89 common DEGs were identified in the gene expression profiles of OA and sarcopenia, including 76 upregulated and 13 downregulated genes. These 89 DEGs were significantly enriched in protein digestion and absorption, the PI3K-Akt signaling pathway, and extracellular matrix-receptor interaction. PPI network analysis and MCC algorithm analysis of the 89 common DEGs identified the top 17 candidate hub genes. Based on the differential expression analysis of these 17 candidate hub genes in the validation datasets, AEBP1 and COL8A2 were ultimately selected as the common key genes for both diseases, both of which showed a significant upregulation trend in the disease groups (all P<0.05). The value of area under the curve (AUC) for AEBP1 and COL8A2 in the OA and sarcopenia datasets were all greater than 0.7, indicating that both genes have potential value in predicting OA and sarcopenia. Real-time RT-PCR results showed that the mRNA expression levels of AEBP1 and COL8A2 were significantly upregulated in the disease groups (all P<0.05), consistent with the results observed in the bioinformatics analysis. GSEA revealed that AEBP1 and COL8A2 were closely related to extracellular matrix-receptor interaction, ribosome, and oxidative phosphorylation in OA and sarcopenia. CONCLUSIONS AEBP1 and COL8A2 have the potential to serve as common biomarkers for OA and sarcopenia. The extracellular matrix-receptor interaction pathway may represent a potential target for the prevention and treatment of both OA and sarcopenia.
Sarcopenia/genetics* ; Osteoarthritis/genetics* ; Computational Biology/methods* ; Humans ; Protein Interaction Maps/genetics* ; Animals ; Mice ; Gene Expression Profiling ; Gene Ontology ; Transcriptome ; Male ; Signal Transduction/genetics* ; Gene Regulatory Networks

OBJECTIVES: Osteoarthritis (OA) is one of the most common chronic degenerative diseases, with chondrocyte apoptosis and extracellular matrix (ECM) degradation as the major pathological changes. The mechanical stimulation can attenuate chondrocyte apoptosis and promote ECM synthesis, but the underlying molecular mechanisms remain unclear. This study aims to investigate the role of primary cilia (PC) in mediating the effects of mechanical stimulation on OA progression. METHODS: In vivo, conditional knockout mice lacking intraflagellar transport 88 (IFT88^flox/flox IFT88 knockout; i.e., primary cilia-deficient mice) were generated, with wild-type mice as controls. OA models were established via anterior cruciate ligament transection combined with destabilization of the medial meniscus, followed by treadmill exercise intervention. OA progression was evaluated by hematoxylin-eosin staining, safranin O-fast green staining, and immunohistochemistry; apoptosis was assessed by TUNEL staining; and limb function by rotarod testing. In vitro, primary articular chondrocytes were isolated from mice and transfected with lentiviral vectors to suppress IFT88 expression, thereby constructing a primary cilia-deficient cell model. Interleukin-1β (IL-1β) was used to induce an inflammatory environment, while cyclic tensile strain (CTS) was applied via a cell stretcher to mimic mechanical loading on chondrocytes. Immunofluorescence and Western blotting were used to detect the protein expression levels of type II collagen α1 chain (COL2A1), primary cilia, IFT88, and caspase-12; reverse transcription polymerase chain reaction was performed to assess COL2A1 mRNA levels; and flow cytometry was used to evaluate apoptosis. RESULTS: In vivo, treadmill exercise significantly reduced Osteoarthritis Research Society International (OARSI) scores and apoptotic cell rates, and improved balance ability in wild-type OA mice, whereas IFT88-deficient OA mice showed no significant improvement. In vitro, CTS inhibited IL-1β-induced ECM degradation and apoptosis in primary chondrocytes; however, this protective effect was abolished in cells with suppressed primary cilia expression. CONCLUSIONS Mechanical stimulation delays OA progression by mediating signal transduction through primary cilia, thereby inhibiting cartilage degeneration and chondrocyte apoptosis.
Animals ; Chondrocytes/cytology* ; Apoptosis/physiology* ; Mice ; Cilia/metabolism* ; Osteoarthritis/pathology* ; Extracellular Matrix/metabolism* ; Mice, Knockout ; Disease Progression ; Interleukin-1beta ; Male ; Cells, Cultured

Objective To explore the role of neogambogic acid in the characteristics of colorectal cancer stem cells (CRC-CSCs) through the Wnt/β-catenin signaling pathway. Methods The colorectal cells SW480 and HCT166 were divided into control group and neogambogic acid groups (1.5, 3, 6, and 12 μmol/L). The viability of CRC-CSCs was determined by MTT method, and spheroid and clone formation assays were used to assess the capacity of spheroid formation and self-renewal ability of the cells. The effects of neogambogic acid on the apoptosis and cell cycle of CRC-CSCs were evaluated by flow cytometry assays. Real-time quantitative PCR was used to detect the mRNA expression levels of relative markers (CD133, CD44, ALDH1, Oct4, and Nanog) of CRC-CSCs, and the protein expression levels of the self-renewal marker (PCNA), apoptosis markers (cleaved caspase-3 and cleaved caspase-9), and Wnt/β-catenin signaling pathway markers (p-GSK3β, GSK3β, β-catenin, and Wnt) were analyzed using Western blot. Results Compared with the control group, after neogambogic acid treatment, the viability of SW480 and HCT116 cells decreased (P<0.05), the spheroid forming ability and the clone numbers of CRC-CSCs decreased (P<0.001, P<0.01) but the cell apoptosis rate increased (P<0.01), and cell cycle was arrested in G₀/G₁ phase. Moreover, neogambogic acid downregulated the mRNA and protein expression of relative markers of CRC-CSCs (CD133, CD44, ALDH1, Oct4, and Nanog), PCNA, p-GSK3β, β-catenin, and Wnt (P<0.05) and upregulated the expression of cleaved caspase-3, cleaved caspase-9, and GSK3β (P<0.01). Conclusion Neogambogic can inhibit the stem cell properties of colorectal cells via inhibition of Wnt/β-catenin signaling pathway. As a result, neogambogic acid may be an attractive agent against colorectal cancer.

Obesity is a risk factor and pathological basis for various chronic non-communicable diseases and is an important risk factor leading to human mortality and disability. The harm of obesity to the body includes not only various systemic diseases but also some ocular diseases. Currently, the higher pursuit of life and visual quality has led to increased attention to the etiology and prevention of ocular diseases, and the impact of obesity on ocular diseases has been gradually discovered. This article reviews the impact of obesity on certain ocular diseases to deepen the understanding of obesity's impact on ocular diseases and provide a reference for the prevention and treatment of ocular diseases.

OBJECTIVE: To analyze the risk factors of hypophosphatemia in patients with acute respiratory distress syndrome (ARDS). METHODS: A retrospective case-control study was conducted. The clinical data of the patients with ARDS admitted to Yanbian University Affiliated Hospital from January 2018 to October 2022 were collected. According to the 1-day serum phosphorus level after intensive care unit (ICU) admission, the patients with normal (0.80-1.45 mmol/L) or elevated (> 1.45 mmol/L) serum phosphorus levels were included in the non-hypophosphatemia group, while those with phosphorus levels lower than 0.80 mmol/L were included in the hypophosphatemia group. The differences in the inflammatory indicators [neutrophils percentage (NEU%), neutrophil count (NEU), lymphocyte count (LYM), high-sensitivity C-reactive protein (hs-CRP)], proteins [total protein (TP), albumin (Alb), prealbumin (PA)], blood lactic acid (Lac), neutrophil/lymphocyte ratio (NLR), neutrophil/albumin ratio (NAR), and blood lactic acid/albumin ratio (L/A) at 1, 2, 4, 6 and 8 days after ICU admission were compared between the two groups. The partial correlation method was used to analyze the correlation between the 1-day serum phosphorus level after ICU admission and the above indicators. Multivariate Logistic regression analysis was adopted to explore the risk factors of hypophosphatemia in patients with ARDS. RESULTS: All 110 patients were enrolled in the final analysis, among which there were 56 cases in the hypophosphatemia group and 54 cases in the non-hypophosphatemia group. At 1 day and 2 days after ICU admission, NEU% in the hypophosphatemia group were significantly higher than those in the non-hypophosphatemia group (1 day: 0.87±0.08 vs. 0.82±0.12, 2 days: 0.87±0.05 vs. 0.83±0.11, both P < 0.05). As the ICU admission time prolonged, LYM in the hypophosphatemia group was basically on the rise, and NEU%, hs-CRP, and NLR were first decreased and then increased. At 1 day after ICU admission, TP, Alb and PA in the hypophosphatemia group were significantly lower than those in the non-hypophosphatemia group [TP (g/L): 52.96±8.42 vs. 56.47±8.36, Alb (g/L): 29.73±5.83 vs. 33.08±7.35, PA (g/L): 69.95±50.72 vs. 121.50±82.42, all P < 0.05]. As the ICU admission time prolonged, TP and Alb in the hypophosphatemia group were basically showed a trend of first decreasing and then increasing, but at 8 days, Alb was still lower than that at 1 day, and PA basically showed an upward trend. In the non-hypophosphatemia group, the change trends of TP and Alb were consistent with those in the hypophosphatemia group. Lac and L/A both showed a downward trend in the two groups. Partial correlation analysis showed that 1-day serum phosphorus level after ICU admission was significantly negatively correlated with NEU% and hs-CRP (r value was -0.229 and -0.286, respectively, both P < 0.05), and significantly positively correlated with LYM and PA (r value was 0.231 and 0.311, respectively, both P < 0.05). Multivariate Logistic regression analysis showed that 1-day NEU% [odds ratio (OR) = 0.932, 95% confidence interval (95%CI) was 0.873-0.996, P = 0.038] and Alb (OR = 1.167, 95%CI was 1.040-1.308, P = 0.008) were the independent risk factors for hypophosphatemia in ARDS patients. CONCLUSION NEU% and Alb at 1 day after ICU admission are independent risk factors for hypophosphatemia in patients with ARDS.
Humans ; Hypophosphatemia/etiology* ; Respiratory Distress Syndrome/blood* ; Risk Factors ; Retrospective Studies ; Case-Control Studies ; Intensive Care Units ; Male ; Female ; Phosphorus/blood* ; Middle Aged ; Neutrophils ; Aged ; C-Reactive Protein

Objective: To design HBV DNA proficiency testing and system comparison samples with different concentration gradients, analyze their detection results in PCR detection systems, evaluate the nucleic acid detection capabilities of laboratories and differences between detection systems, and put forward suggestions for continuous quality improvement to participating laboratories. Methods: Three groups of randomly numbered proficiency testing samples (with HBV DNA reference concentrations of <2, 7.5, and 30 IU/mL respectively) were taken as the detection objects. Using nucleic acid test data from 11 provincial blood station laboratories as the source, the samples were grouped by detection system and laboratory successively, and statistical analysis was conducted. Results: Statistical analysis of the detection data of the three groups of samples based on detection systems and laboratories showed that from low to high concentration, the coincidence rate between the detection results of different detection systems and laboratories and the expected results showed an increasing trend: 38.89%, 85.90%, and 100.00%; the same system exhibited certain differences in performance among different laboratories. Conclusion: Through this proficiency testing and system comparison, it is found that there are certain differences in the detection capabilities of different laboratories and different nucleic acid test systems. Blood station laboratories should standardize processes, strengthen quality management and data analysis on the basis of being familiar with the detection performance of their detection systems, and at the same time strengthen the control of laboratory interference factors to continuously improve the nucleic acid detection capabilities of blood station laboratories.

AIM:To investigate the protective ef-fect of plumbagin(PL)against pulmonary fibrosis(PF)and its possible mechanisms.METHODS:Sixty male C57BL/6 mice were randomly divided into control,bleomycin group(BLM),low dose PL group(1 mg/kg)and high dose PL group(2 mg/kg).The mice PF model was replicated using intratracheal injection of BLM(3 mg/kg),and then PL(1 or 2 mg/kg)was injected intraperitoneally for 3 weeks and the animals were executed.HE and Masson staining were used to observe morphological changes in lung tissue and collagen deposition.The activities or levels of superoxide dismutase(SOD),glutathione(GSH),malondialdehyde(MDA)and hy-droxyproline(HYP)were measured in mouse lung tissue;ELISA for interleukin-6(IL-6)in mouse lung tissue.Immunohistochemical detection of nuclear factor-related factor 2(Nrf2)and reduced nicotin-amide adenine dinucleotide phosphate oxidase 4(NOX4)positive cell expression in mouse lung tis-sue.The expression levels of α-smooth muscle ac-tin(α-SMA),collagen Ⅰ(Col Ⅰ),collagen Ⅲ(Col Ⅲ),IL-6,transforming growth factor-β1(TGF-β1),p-Smad2,Nrf2 and NOX4 were detected by Western blotting.RESULTS:Compared with the BLM group,PL treatment attenuated lung parenchymal and in-terstitial injury and extracellular matrix deposition in mice,reduced HYP content(P＜0.01,P＜0.05),de-creased protein expression of α-SMA,collagen Ⅰand Ⅲ(P＜0.01,P＜0.05),diminished IL-6 secretion(P＜0.01);improved the body's antioxidant capacity(increased SOD and GSH activity and decreased MDA content,P＜0.01,P＜0.05),significantly down-regulated TGF-β1,p-Smad2 and NOX4-positive cells and protein expression(P＜0.01,P＜0.05)and up-regulated Nrf2-positive cells and protein expression(P＜0.01,P＜0.05).CONCLUSION:PL may slow down the PF process by modulating the TGF-β1/Smad2 and Nrf2/NOX4 pathways to attenuate inflammato-ry responses and collagen deposition and improve the body's antioxidant capacity.

Objective:To investigate the changes of pathogenic bacteria distribution and immune response of urinary tract infection(UTI)after pyeloureteroplasty in children.Methods:A total of 150 children with obstructive hydronephroplasty who received pyeloureteroplasty in Qinghai Women and Children's Hospital from February 2020 to June 2023 were selected as the study objects.The postoperative urine of the children was collected,the pathogens were identified by automatic bacterial analyzer,and the patients were divided into infected group and uninfected group according to the infection status.The detection of pathogenic bacteria in children with UTI was analyzed.The clinical data of the two groups were compared,and the influencing factors of postoperative UTI were screened by Logistic regression analysis,and the prediction model was established and verified.The changes of immune response were compared between the two groups.Results:UTI occurred in 56 cases(37.33%)of 150 children who underwent pyeloureteroplasty.There were 58 strains of gram-negative bacteria,29 strains of gram-positive bacteria and 2 strains of fungi isolated.The main pathogenic bacteria was Escherichia coli.Multivariate Logistic regression analysis showed that serum creatinine(SCr)and hydronephrosis volume/renal volume(HV/RV)levels increased,urinary catheter retention time,urinary bag replacement time and hospital stay were risk factors for UTI after pyeloureteroplasty in children,increased age and elevated albumin(Alb)were protective factors(P<0.05).Through Bootstrap self-sampling,the prediction model had good differentiation and accuracy.There was no significant difference in the levels of CD4+,CD8+and IgM between the two groups before surgery(P>0.05),and the levels of CD4+,CD8+and IgM were signi-ficantly improved between the two groups after surgery,and the improvement degree of the uninfected group was significantly better than that of the infected group(P<0.05).Conclusion:The pathogens of UTI in children after pyeloureteroplasty are mainly gram-nega-tive bacteria,and the immune function is increased 7 days after the operation.