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.

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.

ObjectiveTo study the changing law of appearance color and physicochemical properties of Angelicae Sinensis Radix Carbonisata（ASRC） during the processing by color space method combined with statistical analysis， so as to provide reference for determining the processing endpoint and evaluating the quality of the decoction pieces. MethodsTaking processing time（4， 8， 12， 16 min） and temperature（180， 200， 220， 240 ℃） as factors， ASRC decoction pieces with different processing degrees were prepared in a completely randomized design. Then， the brightness value（L^*）， red-green value（a^*）， yellow-blue value（b^*）， and total chromaticity value （E^*ab） of the decoction pieces were determined by spectrophotometer， the color difference value（ΔE） was calculated， and the data of colorimetric values were analyzed by discriminant analysis. At the same time， the pH， charcoal adsorption， and contents of tannins， 5-hydroxymethylfurfural（5-HMF）， tryptophan， chlorogenic acid， ferulic acid， senkyunolide I， senkyunolide H and ligustilide of ASRC with different processing degrees were determined by pH meter， ultraviolet and visible spectrophotometry and ultra-high performance liquid chromatography（UPLC）. Principal component analysis（PCA） was used to analyze the data of physicochemical indexes， after determining the processing technology of ASRC， the canonical discriminant function was established to distinguish the decoction pieces with different processing degrees， and leave-one-out cross validation was conducted. Finally， Pearson correlation analysis was used to explore the correlation between various physicochemical indexes and chromaticity values. ResultsWith the prolongation of the processing time， L^*， a^*， b^* and E^*ab all showed a decreasing trend， and the established discriminant model based on color parameters was able to distinguish ASRC with different processing degrees. The pH showed an increasing trend with the prolongation of processing time， and the charcoal adsorption， and the contents of tannins， 5-HMF， and tryptophan all showed an increasing and then decreasing trend. Among them， the charcoal adsorption， contents of tannin and 5-HMF reached their maximum values successively after processing for 8-12 min. While the contents of chlorogenic acid， ferulic acid， senkyunolide I， senkyunolide H and ligustilide decreased with the increase of processing time， with a decrease of 60%-80% at 8 min of processing. Therefore， the optimal processing time should be determined to be 8-12 min. PCA could clearly distinguish ASRC with different processing degrees， while temperature had no significant effect on the processing degree. The 12 batches of process validation results（10 min， 180-240 ℃） showed that except for 3 batches identified as class Ⅱ light charcoal， all other batches were identified as class Ⅲ standard charcoal， and the chromaticity values of each batch of ASRC were within the reference range of class Ⅱ-Ⅲ sample chromaticity values. The correlation analysis showed that the chromaticity values were negatively correlated with pH and charcoal adsorption， and positively correlated with contents of tryptophan， chlorogenic acid， ferulic acid， senkyunolide I， senkyunolide H， and ligustilide. And both pH and charcoal adsorption were negatively correlated with the contents of the above components， but the charcoal adsorption was positively correlated with the content of 5-HMF. ConclusionThe chromaticity values and the contents of various physicochemical indicators of ASRC undergo significant changes with the prolongation of processing time， and there is a general correlation between chromaticity values and various physicochemical indicators. Based on the changes in color and physicochemical indicators， the optimal processing time for ASRC is determined to be 8-12 min. This study reveals the dynamic changes of the relevant indexes in the processing of ASRC， which can provide a reference for the discrimination of the processing degree and the quantitative study of the processing endpoint.

The development of antiviral drugs targeting SARS-CoV-2 remains a major strategy for the prevention and treatment of COVID-19 infection. Current anti-SARS-CoV-2 agents mainly act on key viral protein targets involved in the viral life cycle, such as the main protease (Mpro), papain-like protease (PLpro), and RNA-dependent RNA polymerase (RdRp). However, these drugs are insufficient to address the challenges posed by the rapid mutation rate and drug resistance of SARS-CoV-2. In recent years, viral RNA has demonstrated to be a highly promising therapeutic target. Small-molecule drugs that target viral RNA possess distinct advantages, featuring novel mechanisms of action and the potential for broad-spectrum antiviral activity as well as the ability to overcome drug resistance. Such agents provide a new avenue for combating coronavirus threats. This review systematically summarizes recent advances in the development of small-molecule inhibitors targeting conserved SARS-CoV-2 RNA structures, including the frameshift stimulation element (FSE), stem-loops (SL), G-quadruplexes (G-4), and RNA-targeting chimeras (RNATAC), aiming to provide some insight to guide future.

Objective To explore the mechanism of myocardial toxicity caused by N-methyl-3,4-methyle-nedioxyamphetamine(MDMA),the changes of intracellular calcium oscillation mode and calcium han-dling proteins during acute exposure to different concentrations of MDMA were detected,and the in-volvement of nuclear factor κB(NF-κB)and its effect on calcium handling proteins were investigated.Methods Primary rat cardiomyocytes were cultured to establish MDMA acute exposure model,and a control group was set up.The MDMA poisoning model was divided into three concentration groups of 10,100 and 1 000 μmol/L.After 1 h of exposure,the morphological changes of cardiomyocytes were ob-served,the cytotoxicity and changes in calcium signals were measured,and the changes in calcium handling proteins RyR2,SERCA2a,PLN,NCX1 and Cav1.2 were detected.The changes of NF-κB activity and the expression of nucleoprotein p-p65(Ser311)and PKCζ after MDMA exposure,and the intervention of NF-κB inhibitors pyrrolidine dithiocarbamate ammonium(PDTC)and protein kinase C(PKC)inhibitor chelerythrine(CHE)were detected by electrophoretic mobility shift assay(EMSA)and Western blotting.The effects of PDTC intervention on calcium signals,and the expressions of RyR2,SERCA2a,PLN,NCX1 and Cav1.2 after acute MDMA exposure were also observed.Results No obvious changes were observed in the morphology of cardiomyocytes after acute exposure to MDMA,whereas the oscillation waveform of intracytoplasmic calcium ion showed irregular changes with increased oscillation amplitude,intense fluctuations,irregular frequency,and increased fluctuation range of relative optical density values.The expression of RyR2,SERCA2a and NCX1 increased,while the expression of Cav1.2 and PLN de-creased.Acute MDMA exposure could increase NF-κB activity,while PDTC and CHE intervention could inhibit NF-κB activity.In MDMA exposed group,the expression of PKCζ and nucleoprotein p-p65(Ser311)both increased and could be inhibited by CHE.After the intervention of PDTC to block NF-κB,the amplitude of calcium oscillation was lower than that of the MDMA exposed group,and the expres-sion of RyR2,SERCA2a and NCX1 decreased.There was no significant change in PLN,while the ex-pression of Cav1.2 increased.Conclusion MDMA can lead to an increase of calcium ion concentration in cardiomyocytes.Calcium ions are involved in myocardial toxicity of MDMA.The mechanism is re-lated to changes in calcium handling proteins,mainly associated with the increased expression of RyR2.MDMA can up-regulate the intracellular activity of NF-κB through the PKCζ-NF-κB pathway and affect calcium handling proteins,which aggravate intracellular calcium overload during acute MDMA exposure.

TCM believes that the main pathogenesis of gastrointestinal dysfunction (GD) after laparoscopic cholecystectomy (LC) is spleen and stomach weakness, liver and stomach disharmony, liver depression and spleen deficiency, and intestinal depression. Moxibustion in the treatment of GD after LC can avoid the aggravation of gastrointestinal burden caused by oral drugs. The intervention methods mainly include suspension moxibustion, umbilical moxibustion, heat sensitive moxibustion, thunder fire moxibustion, warm acupuncture, partition moxibustion, etc. Moxibustion is often performed on the acupoints in liver meridian, spleen meridian, stomach meridian, small intestine meridian, large intestine meridian and Conception Vessel, such as Taichong (LR3), Ganshu (BL18), Yinlingquan (SP9), Zusanli (ST36), Tianshu (ST25), Wangu (SI4), Hegu (LI4), Zhongwan (CV12), Shenque (CV8) and Qihai (CV6). At present, most studies combined with moxibustion on the basis of conventional Western medicine treatment can significantly improve the efficacy, and have certain advantages in improving gastrointestinal motility decline, intestinal flora imbalance, first exhaust time, gastrointestinal hormone level disorder and intestinal mucosal barrier dysfunction. However, there are still some problems in the existing research: small sample size of clinical research, not perfect scoring scale, not unified treatment plan and operation standard, relatively scarce basic research, relatively simple acupoint research, lack of biochemical evaluation indicators, and the research of national moxibustion needs to be explored and improved in the future.

Objective: To investigate prevalence of hepatitis E virus (HEV) infection among voluntary blood donors in Dalian and provide evidence for enhancing blood screening strategies. Methods: A total of 3 277 blood donor samples collected between December 2023 and February 2024 at Dalian Blood Center underwent routine blood screening (ALT, HBsAg, anti-HCV, HIV Ag/Ab, anti-TP, and HBV/HCV/HIV NAT). Subsequently, HEV antigen (Ag) was detected using chemiluminescence immunoassay (CLIA). HEV-Ag reactive samples were further tested for HEV RNA, IgM and IgG antibodies. Blood donors with repeated reactive HEV Ag results were followed up to clarify the status of infection. Results: Among the 3 277 blood donor samples, 6 (0.18%) were repeatedly reactive for HEV Ag. However, supplemental testing for HEV RNA, anti-HEV IgM, and anti-HEV IgG on these samples yielded non-reactive results. One of these six blood donors was successfully followed up. On day 218 after the initial detection of HEV Ag reactivity, HEV Ag, HEV RNA, HEV IgM and IgG antibody were found to be non-reactive. Conclusion: The reaction rate for HEV antigen screening among voluntary blood donors in Dalian is low. CLIA method for detecting HEV antigen is easy to operate and cost-effective, but demonstrates some false reactivity. Improving the specificity of the assay and combining it with nucleic acid testing (NAT) would be valuable for implementing a selective HEV screening strategy for blood donors.