Objective: To establish evidence-based, safe and efficient management of HIV-reactive blood donors by investigating safe and feasible assessment strategies for HIV-reactive blood donors based on routine blood screening data. Methods: The data of blood screening, supplementary testing, follow-up and CDC confirmation for HIV-reactive blood donors in our center from 2014 to 2024 were analyzed systematically to confirm HIV infection and identify infection status. Results: There were 1 235 samples (0.13%, 1 235/928 000) reactive in HIV blood screening over the 11-year period. A-mong them, 199 donors (16.11%) in asymptomatic HIV infection (HIV Ag/Ab++&HIV RNA+), 2(0.16%) as acute early HIV infection (HIV Ag/Ab+-&HIV RNA+) and 7(0.57%) as window-period infection (HIV RNA positive only) were confirmed. Donors with the result of HIV Ag/Ab+-&HIV RNA-(single-positive) were all excluded for HIV infection, while 1 in 6 HIV Ag/Ab++&HIV RNA-donors (double-positive) was confirmed to have HIV infection. When HIV Ag/Ab reagents were used continuously before and after the follow-up, it's observed in one reagent that the proportion of negative results in subsequent follow-up in single-positive donors who had negative results in the first sampling was significantly higher than the proportion of negative results in subsequent follow-up in those initially single-positive (P<0.05). But no significant difference was observed in another reagent (P>0.05). When reagents were changed in follow-up, the rate of singlepositive donors with negative results in the first sampling reached 96.7%, which was significantly higher than the negative rate of those without reagent changing in follow-up (P<0.05). Conclusion: Based on the serological and nucleic acid testing results of HIV blood screening, the confirmation of HIV infection and identification of infection status can be achieved accurately and efficiently. All HIV Ag/Ab+-&HIV RNA-donors were confirmed as false positive, and should be maintained their eligibilities for blood donation, but recommended to pass the retest before next donation. Using a different reagent for retesting helps improve the eligible rate. HIV Ag/Ab++&HIV RNA-donors should be deferred permanently due to the risk of true positivity.

ObjectiveTo explore the diagnostic value of resting-state functional magnetic resonance imaging (rs-fMRI) for mild cognitive impairment (MCI) stage of Alzheimer's disease (AD), and to investigate the changes in brain functional connectivity in default mode network (DMN) and medial temporal lobe (MTL) regions. MethodsLiteratures were retrieved from multiple databases including CNKI, PubMed, Medline, and Embase, etc. from January, 2020 to October, 2025, investigating the changes in functional connectivity of DMN and MTL in patients with MCI compared to health control (HC) using rs-fMRI. Two researchers independently screened and extracted the literatures and methodological quality was assessed using QUADAS-2. Review Manager 5.4 was used to perform a meta-analysis of neuroimaging indicators in MCI patients and HC subjects. Stata and SDM were utilized to summarize diagnostic efficacy and brain functional connectivity, calculating the over all sensitivity, specificity and summary receiver operating characteristic-area under the curve (SROC-AUC). Deeks funnel plots were drawn, literature weights were analyzed, and subgroup analyses were conducted. ResultsA total of ten literatures were ultimately included, involving 1 010 patients with MCI and 1 714 HC subjects. MCI patients showed decreased or abnormal blood oxygen level dependence signals in DMN, focusing on bilateral medial prefrontal cortex (mPFC) and posterior cingulate cortex. The SROC-AUC was 0.91. In MTL, there was a characteristic decrease of spontaneous neural functional connectivities between the hippocampus and other regions, reflecting the obstruction of information transmission from episodic memory to the central nodes. Abnormal functional connectivity in DMN and MTL resulted in compensatory resting-state functional connectivity enhancement in other subnetworks or local functional connections, such as frontoparietal network and the hippocampal-parietal network. Abnormal activation of mPFC suggested atrophy of the hippocampus or abnormal brain function. The decline in functional connectivity between DMN and MTL indicated impairment of memory and information processing in the early stage. ConclusionThe early functional decoupling between DMN and MTL is a crucial neural mechanism at the MCI stage of AD, providing important neuroimaging evidence for the early diagnosis of AD.

Objective:To explore the efficacy of different second-line treatment strategies in the real world after progression of first-line immunotherapy and its combination therapies in patients with driver gene-negative advanced non-small cell lung cancer (NSCLC) .Methods:A retrospective analysis was conducted on the clinical data of 93 driver gene-negative advanced NSCLC patients who received first-line immunotherapy and its combination therapies from January 1, 2018 to December 31, 2023 at the First Affiliated Hospital of Xinxiang Medical University and Xinxiang Central Hospital. Patients were categorized into immune checkpoint inhibitors (ICIs) -resistant ( n=43) and ICIs-responsive ( n=50) groups according to whether progression free survival (PFS) exceeded 6 months after first-line treatment. Patients were categorized into ICIs-treated ( n=55) and non-ICIs-treated ( n=38), anti-angiogenic-treated ( n=51) and non-anti-angiogenic-treated ( n=42) groups according to the different second-line treatment strategies after progression of first-line immunotherapy and its combination therapies. The median PFS2 (mPFS2) and median overall survival (mOS) 2 after second-line treatment of each group were compared. The Kaplan-Meier method was used for survival analysis. Results:The mPFS2 and mOS2 of 93 advanced NSCLC patients who progressed after first-line ICIs treatment were 4.9 months (95% CI: 4.1-5.7 months) and 14.7 months (95% CI: 11.2-18.2 months). The mPFS2 of patients in the first-line ICIs-responsive and ICIs-resistant groups were 6.0 and 3.8 months, respectively, with no statistically significant difference ( χ2=2.00, P=0.157), and the mOS2 were 25.3 and 11.3 months, respectively, with a statistically significant difference ( χ2=12.13, P<0.001). The mPFS2 of patients in the second-line ICIs-treated group and the non-ICIs-treated group were 5.2 and 4.6 months, respectively, with no statistically significant difference ( χ2=0.16, P=0.687). The mOS2 were 15.1 and 12.7 months, respectively, with no statistically significant difference ( χ2=0.01, P=0.930). The mPFS2 of patients in the second-line anti-angiogenic-treated and non-anti-angiogenic-treated groups were 4.5 and 6.0 months, respectively, with no statistically significant difference ( χ2=0.41, P=0.525), the mOS2 were 14.7 and 16.8 months, respectively, with no statistically significant difference ( χ2=0.01, P=0.943) . Conclusions:After progression of first-line ICIs therapy in patients with driver gene-negative advanced NSCLC, first-line ICIs-responsive patients have significantly longer OS after second-line treatment compared with ICIs-resistant patients. The efficacy of second-line therapy in patients after progression of first-line ICIs therapy does not show significant differences due to the type of treatment strategies.

Objective To investigate the therapeutic effects and mechanisms of Aurantii Fructus Immaturus(AFI)on slow-transit constipation(STC)in mice.Methods A STC model was established via intragastric administration of Loperamide Hydrochloride.Successfully modeled mice were randomized into a model group,low-and high-dose AFI groups,a high-dose AFI+Masitinib[tyrosine kinase(c-Kit)inhibitor]group,additionally,a normal group was set up.After intervention,intestinal transit rate,6-hour fecal pellet number,fecal water content,and colonic histomorphology(hematoxylin-eosin staining)were assessed.Enzyme-linked immunosorbent assay(ELISA)was used to measure levels of 5-hydroxytryptamine(5-HT),vasoactive intestinal polypeptide(VIP),substance P(SP),nitric oxide(NO),and nitric oxide synthase(NOS)activity in colon tissue.Quantitative real-time PCR(qRT-PCR)was used to evaluate mRNA expression of stem cell factor(SCF)and c-Kit in colon tissue,Western Blot was used to analyze relative protein expression of aquaporin 3(AQP3),aquaporin 8(AQP8),SCF,and c-Kit in colon tissue.Results Compared with the normal group,there was devere colonic damage observed in the colon tissue of the mice in the model group,the fecal pellet number,fecal water content,intestinal transit rate,colon tissue SP content,c-Kit and SCF gene and protein expression levels were reduced.The contents of 5-HT,VIP and NO,NOS activity and the protein expression levels of AQP3 and AQP8 in colon tissue were increased,and the differences were statistically significant(P＜0.05).Compared with the model group,the colonic injury of mice in the low-and high-does AFI groups showed obvious improvement,the fecal pellet number,fecal water content,intestinal transit rate,colon tissue SP content,c-Kit and SCF gene and protein expression levels were increased,the contents of 5-HT,VIP and NO,NOS activity and the protein expression levels of AQP3 and AQP8 in colon tissue were decreased(P＜0.05).Masitinib partially reversed the laxative effects of AFI(P＜0.05).Conclusion AFI enhances intestinal motility,alleviates colonic injury,and improves defecation in STC mice,potentially via activation of the SCF/c-Kit pathway.

Objective To evaluate the clinical efficacy of tendon-regulating and bone-setting manipulation combined with subtalar joint arthroereisis in the treatment of adolescent flexible flatfoot.Methods A retrospective analysis was conducted on the clinical data of 86 children with flexible flatfoot treated at Dongguan Hospital of Guangzhou University of Chinese Medicine(Dongguan Traditional Chinese Medicine Hospital)between December 2022 and February 2024.Based on pre-treatment physician-patient communication,the children were divided into an trial group(44 cases)and a control group(42 cases).The control group received subtalar joint arthroereisis alone,while the trial group received additional tendon-regulating and bone-setting manipulation just once one day before surgery and once weekly postoperatively for one month,with a follow-up period of no less than 6 months.The Visual Analogue Scale(VAS)pain score,American Orthopaedic Foot & Ankle Society(AOFAS)ankle-hindfoot score,Tegner activity score,radiographic parameters,and static plantar pressure parameters of the two groups were observed before and after surgery.Results(1)Regarding clinical data,all surgeries were successfully completed in both groups.There were no statistically significant differences in perioperative general data,including operative time,hospital stays,and complication rates(P＞0.05).All children were followed up for no less than 6 months.The results showed that at the final follow-up,the VAS pain score,AOFAS ankle-hindfoot score,and Tegner activity score were significantly improved in both groups compared to preoperative values(P＜0.05),and the improvement in the trial group was significantly greater than that in the control group(P＜0.05 or P＜0.01).(2)Regarding radiographic parameters,at the final follow-up,the talonavicular coverage angle(TNCA),talus-first metatarsal angle(T1MT),talus-second metatarsal angle(T2MT)on weight-bearing anteroposterior radiographs,and the Meary angle between the talus and the first metatarsal as well as calcaneal Pitch angle(Pitch angle)on weight-bearing lateral radiographs were significantly improved in both groups compared to preoperative values(P＜0.05).The improvement in Meary angle,T1MT angle,and T2MT angle in the trial group was significantly greater than that in the control group(P＜0.01).However,there were no statistically significant differences in TNCA and Pitch angle between the two groups at the final follow-up(P＞0.05).(3)Regarding plantar pressure testing,at the 1-month postoperative follow-up,the forefoot load increased significantly in both groups compared to preoperative values(P＜0.05),while the midfoot load significantly decreased(P＜0.05).The increase in forefoot load and decrease in midfoot load in the trial group were significantly greater than those in the control group(P＜0.05 or P＜0.01).However,there were no statistically significant differences in hindfoot load between preoperative and postoperative values or between the two groups at the 1-month follow-up(P＞0.05).Conclusion For adolescent flexible flatfoot,tendon-regulating and bone-setting manipulation combined with subtalar joint arthroereisis can effectively restore the arch,improve foot mechanical imbalance,thereby correcting flatfoot deformity and enhancing joint motor function.

Oral submucous fibrosis (OSF), characterized by excessive deposition of extracellular matrix (ECM) that causes oral mucosal tissue sclerosis, and even cancer transformation, is a chronic, progressive fibrosis disease. However, despite some advancements in recent years, no targeted antifibrotic strategies for OSF have been approved; likely because the complicated mechanisms that initiate and drive fibrosis remain to be determined. In this review, we briefly introduce the epidemiology and etiology of OSF. Then, we highlight how cell-intrinsic changes in significant structural cells can drive fibrotic response by regulating biological behaviors, secretion function, and activation of ECM-producing myofibroblasts. In addition, we also discuss the role of innate and adaptive immune cells and how they contribute to the pathogenesis of OSF. Finally, we summarize strategies to interrupt key mechanisms that cause OSF, including modulation of the ECM, inhibition of inflammation, improvement of vascular disturbance. This review will provide potential routes for developing novel anti-OSF therapeutics.
Humans ; Oral Submucous Fibrosis/immunology* ; Extracellular Matrix/metabolism* ; Myofibroblasts

Pulpitis is a common infective oral disease in clinical situations. The regulatory mechanisms of immune defense in pulpitis are still being investigated. Osteomodulin (OMD) is a small leucine-rich proteoglycan family member distributed in bones and teeth. It is a bioactive protein that promotes osteogenesis and suppresses the apoptosis of human dental pulp stem cells (hDPSCs). In this study, the role of OMD in pulpitis and the OMD-induced regulatory mechanism were investigated. The OMD expression in normal and inflamed human pulp tissues was detected via immunofluorescence staining. Intriguingly, the OMD expression decreased in the inflammatory infiltration area of pulpitis specimens. The cellular experiments demonstrated that recombined human OMD could resist the detrimental effects of lipopolysaccharide (LPS)-induced inflammation. A conditional Omd knockout mouse model with pulpal inflammation was established. LPS-induced inflammatory impairment significantly increased in conditional Omd knockout mice, whereas OMD administration exhibited a protective effect against pulpitis. Mechanistically, the transcriptome alterations of OMD overexpression showed significant enrichment in the nuclear factor-κB (NF-κB) signaling pathway. Interleukin-1 receptor 1 (IL1R1), a vital membrane receptor activating the NF-κB pathway, was significantly downregulated in OMD-overexpressing hDPSCs. Additionally, the interaction between OMD and IL1R1 was verified using co-immunoprecipitation and molecular docking. In vivo, excessive pulpal inflammation in Omd-deficient mice was rescued using an IL1R antagonist. Overall, OMD played a protective role in the inflammatory response via the IL1R1/NF-κB signaling pathway. OMD may optimize the immunomodulatory functions of hDPSCs and can be used for regenerative endodontics.
Pulpitis/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction ; Humans ; Mice ; Mice, Knockout ; Dental Pulp/metabolism* ; Disease Models, Animal ; Lipopolysaccharides

OBJECTIVE: Exploring the formation and aggregation of human islet amyloid polypeptide (hIAPP) (amylin) fibers is significant for promoting the prevention and treatment of type II diabetes mellitus (T2DM). Flavones in pomelo peel have visible biological activity in the anti-diabetes aspect. The present study aimed to investigate the effects of five flavones [naringin (NRG), narirutin (NRR), nobiletin (NOB), sinensetin (SIN), and neohesperidin (NHP)] in pomelo peel on peptide aggregation and explore its possible mechanisms. The cell viability of flavones against peptide aggregation was also evaluated. METHODS: The thioflavin T (ThT) assay and transmission electron microscopy (TEM) were used for evaluating the inhibition and disaggregation of flavones on peptide aggregation. The interaction mechanism was analyzed by endogenous fluorescence, molecular dynamics (MD) simulations, ultraviolet spectroscopy (UV) and isothermal titration calorimetry (ITC) experiments. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and immune assays were performed to characterize the cell viability of flavones against peptide aggregation. RESULTS: The five flavones showed a decrease in fluorescence intensity, fiber number and size under incubation with different molar ratios of hIAPP. The compounds can bind to the aromatic tyrosine (Tyr) residueTyr 37, resulting in the intrinsic fluorescence quenching of the peptides. Five flavones can form hydrogen bonds with hIAPP, which is likely to be based on their phenolic hydroxyl structure. They showed strong binding affinity with peptides. The reaction system of NRG and NRR observed an exothermic reaction, and the others were endothermic reactions. The absorption peaks of the compounds with hIAPP changed and showed hypochromic effects, indicating that there may be π-π stacking interaction. Flavones noticeably increased the cell viability in the presence of amyloid peptides and reduced the absorption intensity induced by peptide oligomers. CONCLUSION A total of five flavones in pomelo peel have inhibitory and depolymerization effects on amyloid fibrils, and can significantly protect cells from the toxic effect of hIAPP and reduce the production of toxic oligomers.

Diabetic cardiomyopathy (DCM) is a medical condition characterized by cardiac remodeling and dysfunction in individuals with diabetes mellitus. Sarcoplasmic reticulum (SR) and mitochondrial Ca²⁺ overload in cardiomyocytes have been recognized as biological hallmarks in DCM; however, the specific factors underlying these abnormalities remain largely unknown. In this study, we aimed to investigate the role of a cardiac-specific long noncoding RNA, D830005E20Rik (Trdn-as), in DCM. Our results revealed the remarkably upregulation of Trdn-as in the hearts of the DCM mice and cardiomyocytes treated with high glucose (HG). Knocking down Trdn-as in cardiac tissues significantly improved cardiac dysfunction and remodeling in the DCM mice. Conversely, Trdn-as overexpression resulted in cardiac damage resembling that observed in the DCM mice. At the cellular level, Trdn-as induced Ca²⁺ overload in the SR and mitochondria, leading to mitochondrial dysfunction. RNA-seq and bioinformatics analyses identified calsequestrin 2 (Casq2), a primary calcium-binding protein in the junctional SR, as a potential target of Trdn-as. Further investigations revealed that Trdn-as facilitated the recruitment of METTL14 to the Casq2 mRNA, thereby enhancing the m⁶A modification of Casq2. This modification increased the stability of Casq2 mRNA and subsequently led to increased protein expression. When Casq2 was knocked down, the promoting effects of Trdn-as on Ca²⁺ overload and mitochondrial damage were mitigated. These findings provide valuable insights into the pathogenesis of DCM and suggest Trdn-as as a potential therapeutic target for this condition.
Animals ; Diabetic Cardiomyopathies/pathology* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac/metabolism* ; Mice ; Calsequestrin/genetics* ; Calcium/metabolism* ; Male ; Sarcoplasmic Reticulum/metabolism* ; Methyltransferases/metabolism* ; Mice, Inbred C57BL ; Mitochondria, Heart/metabolism* ; Disease Models, Animal ; Mitochondria/metabolism*

Lung transplantation is currently the only recognized effective treatment for end-stage lung disease and has improved the quality of life for patients. However, lung transplantation still faces many challenges, including rejection, infection, post-transplant acute kidney injury, post-transplant diabetes mellitus, ischemia-reperfusion injury and donor shortage, etc. Chinese lung transplantation scholars made a series of important progress in the field of clinical research in 2024, focusing on the study and solution of the above problems, and providing new ideas for lung transplantation surgery. This article systematically reviews the clinical research and technological innovation in the field of lung transplantation in 2024, summarizes the achievements of clinical research in the field of lung transplantation in China in 2024, and aims to providing new directions and strategies for future research.