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.

Objective: To explore the management of blood donors tested reactive to HCV in blood screening based on confirmation of HCV infection. Methods: Multiple HCV antibody assays, repeating HCV RNA testing, follow-up of blood donors and retesting of archive samples were performed to confirm HCV infection, identify infection status, and exclude false positives in blood donors reactive to HCV in blood screening. Results: From 2011 to 2024, the unqualified rate of HCV detection in blood screening was 2.45‰(2 751/1 122 026). Among these, anti-HCV+-&NAT-accounted for 1.85‰, followed by anti-HCV++ at 0.60‰. The proportion of anti-HCV+-&NAT-and HCV RNA yields was extremely low (0.007‰). The positive rate of anti-HCV+-&NAT-samples tested by electrochemiluminescence method (ELCIA) was approximately 7.5%, differing among reagents (P<0.05). The follow-up of anti-HCV+-&NAT-donors showed that 96.2% (202/210) were false positives, but 51.4% of donors remained anti-HCV+-&NAT-during follow-up. Among them, 8 donors (3.8%) could not be ruled out from HCV infection due to positive retesting by ELCIA. Of the anti-HCV+-&NAT-donors who were reactive at the first follow-up, 86.8% remained anti-HCV+-&NAT-at the second follow-up. The sampling confirmation data showed that all of 260 anti-HCV++ donors were confirmed as anti-HCV positive, and the proportion of false positives or missed detections by NAT was very low. Two occult HBV infections (OBIs) and one HBsAg carrier were identified among the 3 anti-HCV +-&NAT+ donors, and no HCV infection was confirmed in 5 anti-HCV--&HCV RNA + donors. Conclusion: The prevalence of HCV among blood donors in Dalian was about 0.06%, with extremely low proportion of window-period infection and slightly higher proportion of resolved infections than that of current infections. The majority of anti-HCV+-&NAT-were false positive. Blood donors confirmed as false positive should be qualified in blood screening 3 months later before next donation. In order to reduce the false positive results, it was advisable to avoid the same type of supplementary reagents as the initial reagents when performing confirmation.

Objective: To evaluate repeated testing on blood screening platforms in confirmation of non-discriminatory reactive (NDR) samples in nucleic acid testing (NAT). Methods: A total of 102 HBsAg-negative/NAT NDR samples were collected from voluntary blood donors at Dalian Blood Center between January 2021 and December 2023. Repeated testing was performed using two NAT platforms (Cobas s201 and Panther). For the first round of repeated testing, all samples were tested 12 times on each system; for the second round, the samples which were non-reactive or only reactive once in the first round were tested an additional 8 times. Anti-HBc and anti-HBs was detected using electrochemiluminescence assay (ECA). Meanwhile, blood donors were followed up. Results: The proportion of anti-HBc+ in 102 NDR samples was 88.2%. Forty-one samples (40.2%, 41/102) and 7 samples were confirmed HBV DNA+ in first-round and second-round repeated testing, respectively. The cumulative confirmation rate of HBV DNA+ was 47.1% (48/102) after repeated testing. Extra five blood donors detected HBV DNA+ in follow-up were identified as anti-HBc+ occult hepatitis B virus infection (OBI), while no window period infection was observed. Ultimately, there were 53 HBV infected donors confirmed, 46 HBV infection-unconfirmed, and 3 HBV uninfected. No significant difference was observed between the confirmation rate of the first-round testing and the cumulative confirmation rate after the second-round testing (P>0.05). The proportion of anti-HBc+ donors was quite high in both HBV infection-confirmed (98.1%) and unconfirmed group (82.6%), and donors with seronegative and anti-HBs-only occupied a high proportion in the latter (P<0.05). Conclusion: Numerous repeated testing of NDR samples using NAT platforms cannot achieve complete confirmation of HBV infection. Supplementary anti-HBc testing can minimize potential OBI risk among NDR donors, and is low-cost and efficient.

Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

According to traditional Chinese medicine （TCM） theory， impaired spleen transportation function disrupts nutrient distribution， causing metabolic accumulation of lipids that transform into pathogenic phlegm-dampness. These pathological factors disseminate through the San Jiao and obstruct meridian pathways， ultimately forming the pathogenesis described as "all disorders involve phlegm". Phlegm and dampness share common pathogenic origins but manifest distinct clinical manifestations. Dampness， as the precursor， may congeal into phlegm， while existing phlegm accumulation can further exacerbate dampness stagnation， thereby establishing a self-perpetuating pathological cycle. Modern medical research has confirmed that the essence of "phlegm-dampness" syndrome is closely associated with energy metabolism disorders， serving as a common pathological basis for metabolic syndrome， type 2 diabetes mellitus， atherosclerosis， and other major chronic diseases. As a crucial vehicle for medical experimental research， disease-syndrome combination animal models serve as an indispensable means to advance the modernization of TCM. Currently， based on classical theories such as "rich and greasy foods produce phlegm" and "physical coldness combined with cold consumption causes external pathogens to invade the skin and hair， thereby generating internal dampness"， researchers primarily employ two paradigms to construct animal models of phlegm-turbidity， dampness obstruction， and phlegm-dampness syndromes： the first involves simulating TCM etiological factors （through methods like dietary irregularities， imblanace between work and rest， and combined internal-external dampness exposure）， while the second combines disease with syndrome differentiation （inducing pathological changes through physical， chemical， or biological interventions）. Through comprehensive evaluation incorporating macroscopic observation and microscopic index detection， model animals undergo systematic biological and pathological assessment， with further syndrome type verification achieved via the "prescription-based syndrome detection" approach. However， existing models still exhibit significant deficiencies in both the standardization of modeling methodologies and the systematization of evaluation criteria. This paper reviews the strategies for constructing "phlegm-dampness" syndrome animal models and their corresponding evaluation indices， focusing on the pathological correlations among different modeling approaches. The aim is to provide methodological guidance for research on TCM syndromes related to "phlegm-dampness" syndrome and to support the development of TCM therapies for resolving phlegm and eliminating dampness. This study not only contributes to advancing the standardization of TCM syndrome research but also provides crucial technical support for the modernization of TCM.

BACKGROUND: Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China. METHODS: The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model. RESULTS: During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437). CONCLUSIONS Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.

Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis (OA), but directly modulating mitochondria in vivo remains a significant challenge. This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients, highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA. Consequently, we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool (FoxO3) and integrated it within a nanoengineered 'truck' (NETT, FoxO3-NETT). This was further encapsulated in injectable hydrogel microspheres (FoxO3-NETT@SMs) to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes. Collectively, these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway. As a result, FoxO3-NETT@SMs stimulate chondrocytes proliferation, migration, and ECM production in vitro, and effectively alleviate OA progression in vivo, demonstrating significant potential for clinical applications.

[This corrects the article DOI: 10.1016/j.apsb.2018.08.009.].

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*