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.

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.

ObjectiveThis paper aims to investigate the traditional Chinese medicine syndrome types in patients with chronic hepatitis B （CHB） complicated by metabolic dysfunction-associated fatty liver disease （MAFLD） and explore the correlations between these syndrome types and clinical indicators， as well as ocular manifestation characteristics， thereby providing a reference for syndrome differentiation and treatment strategies in traditional Chinese medicine. MethodsGeneral data， information from the four diagnostic methods of traditional Chinese medicine， clinical indicators， and ocular manifestation data were collected from 506 patients with CHB complicated by MAFLD enrolled at the Public Health Clinical Center of Chengdu between June 2024 and December 2024. Cluster analysis， principal component analysis， and complex network models were employed to identify the distribution patterns of traditional Chinese medicine syndromes. Correlations between different syndrome types and clinical indicators， as well as ocular manifestation characteristics， were further analyzed. ResultsThe predominant syndromes identified in patients with CHB complicated by MAFLD were dampness and heat accumulation （51.58%）， liver depression with spleen deficiency （31.62%）， blood stasis obstructing collaterals （8.89%）， and Qi-Yin deficiency （7.91%）. No statistically significant differences were found among the four syndrome types in routine blood tests and liver function indicators. However， patients with the dampness and heat accumulation type exhibited significantly higher levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， liver stiffness measurement （LSM）， controlled attenuation parameter （CAP）， and alpha-fetoprotein （AFP）， along with lower levels of high-density lipoprotein cholesterol （HDL-C）， compared with those with other syndrome types. Regarding ocular manifestations， the incidence of moon halo signs was significantly higher in patients with the blood stasis obstructing collaterals type than in those with other syndrome types. Additionally， the incidence in scleral zone 3 （corresponding to the large intestine） was higher in patients with the damp and heat accumulation type. ConclusionDampness and heat accumulation is the core syndrome type in patients with CHB complicated by MAFLD， commonly accompanied by spleen deficiency， liver depression， blood stasis， and Yin deficiency. A complex syndrome pattern characterized by a predominance of dampness and heat， along with a mixture of deficiency and excess， is formed. Different traditional Chinese medicine syndrome types are associated with distinct clinical indicators and ocular manifestation characteristics. Among them， patients with the dampness and heat accumulation type exhibit more pronounced metabolic disturbances and liver injury， whereas those with the blood stasis type show a higher incidence of moon halo signs. Abnormalities in scleral zone 3 are also more prevalent in patients with dampness and heat type.

This study aimed to investigate the mechanism of liquiritin (LQ) in the improvement of ventricular remodeling (VR) after acute myocardial infarction (AMI). Molecular docking was used to predict the binding affinity of liquiritin to thioredoxin-interacting protein (TXNIP). After 2 weeks of modeling, the rats were randomly divided into a model group, a low-dose liquiritin group (20 mg/kg LQ), and a high-dose liquiritin group (40 mg/kg LQ). Liquiritin was administered by gavage once a day, and the sham group and model group were given the same volume of 0.5% sodium carboxymethylcellulose (CMC-Na), with intervention of 4 consecutive weeks. Echocardiography was employed to detect the cardiac function, HE staining was used to observe cardiological changes, ELISA was used to detect the activity of serum creatine kinase-MB (CK-MB) activity, and the colorimetric method was adopted to detect serum malondialdehyde (MDA), total superoxide dismutase (T-SOD) and catalase (CAT) activities. RT-qPCR was used to detect the gene expressions of TXNIP, thioredoxin (TRX) and NACHT, LRR, and PYD domains-containing protein 3(NLRP3). Western blot was used to detect the protein expressions of TXNIP, TRX and NLRP3 in rat myocardial tissue. Molecular docking results showed that liquiritin had a good binding affinity to TNXIP target. After 20 and 40 mg/kg liquiritin intervention, the levels of ejection fraction (EF) and fractional shortening (FS) were significantly increased (P<0.01), and the levels of LVIDs, LVIDd, LVESV, and LVEDV were decreased (P<0.01). The myocardial structure was significantly improved, the cell arrangement tended to be regular, and the area of inflammatory cell infiltration and necrosis was reduced. Liquiritin significantly reduced the level of CK-MB (P<0.01), decreased the activity of MDA, and increased the activities of CAT and T-SOD (P<0.01). Liquiritin effectively inhibited the overexpression of TXNIP and NLRP3 genes and proteins, and enhanced the expression of TRX genes and proteins in the myocardial tissues of AMI rats. In conclusion, liquiritin has a regulatory effect on the TXNIP/TRX signaling pathway, inhibits the activation of the NLRP3 inflammasome, and thus improves ventricular remodeling after acute myocardial infarction.

Xiaoji Yinzi is one of the classic prescriptions for treating urinary diseases， originated from the Yan's Prescriptions to Aid the Living （Yan Shi Ji Sheng Fang） written by YAN Yonghe in the Song dynasty. Xiaoji Yinzi is composed of Rehmanniae Radix， Cirsii Herba， Talcum， Akebiae Caulis， Typhae Pollen， Nelumbinis Rhizomatis Nodus， Lophatheri Herba， Angelicae Sinensis Radix， Gardeniae Fructus， and Glycyrrhizae Radix et Rhizoma and has the effects of cooling blood and stopping bleeding， draining water and relieving stranguria. The medical experts of later generations have inherited the original prescription recorded in the Yan's Prescriptions to Aid the Living， while dispute has emerged during the inheritance of this prescription. In this study， the method of bibliometrics was employed to review and analyze the ancient documents and modern clinical studies involving Xiaoji Yinzi. The results showed that Xiaoji Yinzi has two dosage forms： powder and decoction. According to the measurement system in the Song Dynasty， the modern doses of hers in Xiaoji Yinzi were transformed. In the prepration of Xiaoji Yinzi powder， 149.2 g of Rehmanniae Radix and 20.65 g each of Cirsii Herba， Talcum， Akebiae Caulis， stir-fried Typhae Pollen， Nelumbinis Rhizomatis Nodus， Lophatheri Herba， wine-processed Angelicae Sinensis Radix， stir-fried Gardeniae Fructus， and stir-fried Glycyrrhizae Radix et Rhizoma are grounded into fine powder with the particle size of 4-10 meshes and a decocted with 450 mL water to reach a volume of 240 mL. After removal of the residue， the decoction was taken warm before meals， 3 times a day （i.e.， 7.77 g Rehmanniae Radix and 0.97 g each of the other herbs each time）. In the preparation of Xiaoji Yinzi decoction， 20.65 g each of the above 10 herbs are used， with stir-fried Typhae Pollen， wine-processed Angelica Sinensis Radix， stir-fired Gardeniae Fructus， stir-fired Glycyrrhizae Radix et Rhizoma， and raw materials of other herbs. Xiaoji Yinzi is specialized in treating hematuresis and blood stranguria due to heat accumulation in lower energizer， which causes injury of the blood collaterals of gallbladder and dysfunction of Qi transformation. In modern clinical practice， Xiaoji Yinzi is specifically used for treating urinary diseases and can be expanded to treat diseases of the cardiovascular system and other systems according to pathogenesis. The comprehensive research on the key information could provide a scientific reference for the future development of Xiaoji Yinzi.

Objective To establish mouse models exposed to different doses of neodymium oxide via tracheal instillation,and to investigate the mechanisms underlying brain tissue damage induced by neodymium oxide exposure in mice.Methods Forty-eight male C57/BL6 mice were randomly assigned to four groups:the control group,the low-dose group,the medium-dose group,and the high-dose group.The low-dose,medium-dose,and high-dose groups received 62.5 mg/mL,125 mg/mL,and 250 mg/mL neodymium oxide,respectively,via non-exposed tracheal instillation.The control group received an equivalent volume of saline using the same administration method.After 35 days,the mice were euthanized,and brain tissues were collected.RT-PCR was used to assess the mRNA expression changes of Claudin-5 and Occludin.Western blot analysis was performed to evaluate the expression changes of Claudin-5 and Occludin tight junction proteins,as well as the expression changes of MMP-2 and MMP-9 in the brain tissues.Additionally,the expression of the RhoA/ROCK2 signaling pathway and downstream cofilin protein was examined.Changes in oxidative stress markers,including MDA,T-AOC,and NO,were measured using a kit method.Results The mRNA expression of Claudin-5 was significantly reduced in the middle-dose and high-dose groups compared to the control group(P<0.05).Similarly,the mRNA expression of Occludin was significantly lower in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).Additionally,the protein expression of Claudin-5,MMP-2,and Occludin was significantly decreased in the low-dose,medium-dose,and high-dose groups compared to the control group(P<0.05).The protein expression of MMP-9 and RhoA was also signifi-cantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05).Furthermore,the protein expression of ROCK2 and p-cofilin in the high-dose group was significantly lower than that in the control group(P<0.05).The content of MDA and T-AOC was significantly lower in the medium-dose and high-dose groups compared to the control group(P<0.05),and the content of NO in the high-dose group was significantly lower than that in the control group(P<0.05).Conclusion Exposure to neodymium oxide results in increased permeability of the blood-brain barrier in mice,leading to oxidative stress,inflammatory responses,and activation of the RhoA/ROCK2 signaling pathway.

In view of the characteristics of H5N6 subtype avian influenza virus(AIV)that it has both high pathogenicity and the risk of cross-species transmission,posing a serious threat to the poultry farming industry and public health security,in order to effectively prevent and control the spread of H5N6 avian influenza,a rapid,sensitive and specific detection technolo-gy was established in this study.The specific monoclonal antibodies against the neuraminidase N6 protein of avian influenza A virus subtype H5N6 were obtained through hybridoma and monoclonal antibody technology.These antibodies were coupled and labeled with carboxyl-functionalized fluorescent quantum dots,along with previously prepared specific antibodies against the hemagglutinin H5 protein.A rapid fluorescence immunochromatographic detection method for the H5N6 subtype of avian influ-enza virus was established according to the principle of double-antibody sandwich immunochromatography.This method a-chieved a detection sensitivity of 1 ng/mL for recombinant hemagglutinin H5 subtype protein and 0.1 ng/mL for recombinant neuraminidase N6 subtype protein.Moreover,the method exhibited no cross-reactivity with other influenza subtypes or patho-gens,such as Newcastle disease(ND),infectious bronchitis(IB),and infectious laryngotracheitis(ILT),thus demonstrating good specificity.The method effectively identified the highly pathogenic avian influenza virus H5 subtype and directly distin-guished the H5N6 subtype with good accuracy.The fluorescent quantum dot immunochromatographic typing detection method established herein met the sensitivity,specificity,and accuracy requirements for H5N6 subtype detection,and can be further used for rapid detection of the H5 and H5N6 subtypes of avian influenza virus.

Natural antimicrobial peptides(AMPs)are promising candidates for the development of a new gener-ation of antimicrobials to combat antibiotic-resistant pathogens.They have found extensive applications in the fields of medicine,food,and agriculture.However,efficiently screening AMPs from natural sources poses several challenges,including low efficiency and high antibiotic resistance.This review focuses on the action mechanisms of AMPs,both through membrane and non-membrane routes.We thoroughly examine various highly efficient AMP screening methods,including whole-bacterial adsorption binding,cell membrane chromatography(CMC),phospholipid membrane chromatography binding,membrane-mediated capillary electrophoresis(CE),colorimetric assays,thin layer chromatography(TLC),fluorescence-based screening,genetic sequencing-based analysis,computational mining of AMP data-bases,and virtual screening methods.Additionally,we discuss potential developmental applications for enhancing the efficiency of AMP discovery.This review provides a comprehensive framework for identifying AMPs within complex natural product systems.