Background: Our genomic understanding of lymphomas, a heterogeneous group of neoplasms, has grown exponentially. The latest World Health Organization (WHO) and International Consensus classifications reflect the importance of genetic assessment in the diagnosis and prognostication of and therapeutic decision making in lymphoid neoplasms. To address this clinical need for routinely available and timely testing, we aimed to validate the Ion AmpliSeq Liverpool Lymphoid Network Panel (IALLNP; Thermo Fisher Scientific, Waltham, MA, USA). Methods: We clinically validated the IALLNP on the Ion Torrent Genexus Sequencer (Thermo Fisher Scientific). The panel detects single-nucleotide variants (SNVs) and insertions/deletions (indels) in 60 clinically relevant genes. The validation set included a commercial control and 54 DNA samples covering the spectrum of clinically aggressive and indolent lymphomas. Results: After optimizing for poor coverage regions, recurrent artifacts, and false-negative calls, the panel showed good performance in terms of depth of coverage, on-target reads, and uniformity. Its sensitivity for SNVs and indels at a lower limit of detection of 5% variant allele frequency (VAF) was 100%. Specificity in variant-negative samples was 100%, and the mean per-sample number of false-positive variants—which were easily identifiable and excluded upon interrogation of raw data—was 0.4. The panel demonstrated 92.8% reproducibility; however, all nonreproducible variants fell below the 5% VAF analytical threshold. Conclusions The IALLNP is an accurate and reproducible next-generation sequencing panel that delivers genetic results for lymphoid neoplasms in a clinically meaningful timeframe.

Artificial liver support therapy for liver failure is often complicated by thrombocytopenia， which increases the risk of bleeding. This article systematically elaborates on the pathophysiological role of platelets in liver disease， and systematically analyzes the differential effect of various artificial liver support modalities on platelets， with a focus on key factors such as biocompatibility and anticoagulation strategies. This article also summarizes the clinical management approaches including individualized platelet transfusion and the application of thrombopoietic agents and discusses the value of platelet count as a predictive indicator for treatment safety and efficacy， in order to provide a basis for precise clinical intervention.

Objective To evaluate the impact of incorporating two doses of varicella vaccine into the immunization program in Shanghai on the incidence of varicella, age-specific incidence, and varicella outbreaks in kindergartens and schools in Jinshan District, and to assess its prevention and control effects. Methods Descriptive epidemiological methods were used to analyze and compare the population distribution characteristics and the occurrence of varicella outbreaks before (2013-2017) and after (2018-2024) the implementation of the strategy. Interrupted time series (ITS) design and its segmented regression model were used to analyze the changes in the incidence of varicella in the two stages before and after the implementation of the vaccination of two doses of varicella vaccine, and to evaluate the short-term and long-term preventive and control effects of the strategy. Results After the incorporation of two doses of varicella vaccine into the immunization program, the average annual incidence of varicella in Jinshan District decreased from 82.19/100 000 (2013-2017) to 53.51/100 000 (2018-2024). The interrupted time series analysis showed that after the implementation of the strategy, the slope change in the incidence of varicella was -10.20/100 000 (t=-2.38, P=0.04), and the overall trend was downward (slope β₁+β₃= -8.34/100 000). Except for the 30-49 years old group, the incidence rates in all other age groups decreased to varying degrees. Among them, the 5-9 years old group had a better vaccine efficacy (VE) of 52.23% (95% CI: 49.07-60.65), followed by the 10-14 years old group. The number of potential varicella outbreaks and cluster outbreaks in nurseries, kindergartens, and schools across the district dropped significantly. Conclusion Incorporating two doses of varicella vaccine into the immunization program can effectively reduce the incidence of varicella and the number of varicella outbreaks in kindergartens and schools, which is of great significance for the prevention and control of varicella.

Esophageal cancer is one of the malignant tumors that poses a threat to human health, with both high incidence and malignancy. Currently, surgery following neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal cancer; however, the long-term prognosis remains unsatisfactory. In recent years, inhibitors of programmed death protein-1 (PD-1) and its ligand (programmed death ligand-1, PD-L1) have achieved breakthrough progress in other solid tumors, and research on esophageal cancer is gradually being conducted. With the demonstration of good efficacy of PD-1/PD-L1 inhibitors in the first-line and second-line treatment of advanced unresectable esophageal cancer, their incorporation into neoadjuvant treatment regimens has become a hot topic. Therefore, this article reviews the mechanism of action of PD-1/PD-L1 inhibitors and their application in the neoadjuvant treatment of esophageal cancer.

In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*

The phase changes and quantity-quality transfer of 17 batches of Ostreae Concha(Ostrea rivularis) during the raw material-calcined decoction pieces-standard decoction process were analyzed. The content of calcium carbonate(CaCO_3), the main component, was determined by chemical titration, and the extract yield and transfer rate were calculated. The CaCO_3 content in the raw material, calcined decoction pieces, and standard decoction was 94.39%-98.80%, 95.03%-99.22%, and 84.58%-90.47%, respectively. The process of raw material to calcined decoction pieces showed the yield range of 96.85% to 98.55% and the CaCO_3 transfer rate range of 96.92% to 99.27%. The process of calcined decoction pieces to standard decoction showed the extract yield range of 2.86% to 5.48% and the CaCO_3 transfer rate range of 2.59% to 5.13%. The results of X-ray fluorescence(XRF) assay showed that the raw material, calcined decoction pieces, and standard decoction mainly contained Ca, Na, Mg, Si, Br, Cl, Al, Fe, Cr, Mn, and K. The chemometric results showed an increase in the relative content of Cr, Fe, and Si from raw material to calcined decoction pieces and an increase in the relative content of Mg, Al, Br, K, Cl, and Na from calcined decoction pieces to standard decoction. X-ray diffraction(XRD) was employed to establish XRD characteristic patterns of the raw material, calcined decoction pieces, and standard decoction. The XRD results showed that the main phase of all three was calcite, and no transformation of crystalline form or generation of new phase was observed. Fourier transform infrared spectroscopy(FTIR) was employed to establish the FTIR characteristic spectra of the raw material, calcined decoction pieces, and standard decoction. The FTIR results showed that the raw material had internal vibrations of O-H, C-H, C=O, C-O, and CO■ groups. Due to the loss of organic matter components after calcination, no information about the vibrations of C-H, C=O, and C-O groups was observed in the spectra of calcined decoction pieces and standard decoction. In summary, this study elucidated the quantity-quality transfer and phase changes in the raw material-calcined decoction pieces-standard decoction process by determining the CaCO_3 content, calculating the extract yield and transfer rate, and comparing the element changes, FTIR characteristic spectra, and XRD characteristic pattern. The results were reasonable and reliable, laying a foundation for the subsequent process research and quality control of the formula granules of calcined Ostreae Concha(O. rivularis Gould), and providing ideas and methods for the quality control of the whole process of raw material-decoction pieces-standard decoction-formula granules of Ostreae Concha and other testacean traditional Chinese medicine.
Drugs, Chinese Herbal/isolation & purification* ; Calcium Carbonate/analysis* ; Quality Control

The study aims to investigate the impacts of prolyl oligopeptidase (POP) on the replication of foot-and-mouth disease virus (FMDV) in BHK-21 cells. Firstly, the effects of FMDV replication on POP expression in BHK-21 cells were analyzed by Western blotting and Real-time reverse transcription polymerase chain reaction (RT-qPCR). Secondly, a eukaryotic expression plasmid for POP was constructed, and the effects of POP overexpression on the replication of two different serotypes of FMDV were assessed by Western blotting, RT-qPCR, and virus titer assays. Thirdly, specific small interfering RNAs (siRNAs) targeting POP were synthesized, and their efficiency in interfering with endogenous POP expression was identified by RT-qPCR. The impacts of downregulating endogenous POP expression on FMDV replication were further evaluated by Western blotting, RT-qPCR, and virus titer assays. The results indicated that FMDV infection did not significantly affect POP expression in BHK-21 cells. Overexpression of POP dose-dependently enhanced the replication of both FMDV/O and FMDV/A serotypes. Conversely, siRNA-mediated downregulation of endogenous POP expression markedly suppressed FMDV/O replication. This study is the first to demonstrated that the role of the host POP protein in promoting FMDV replication in BHK-21 cells, thereby providing a critical theoretical foundation and potential molecular targets for developing efficient candidate cell strains for foot-and-mouth disease inactivated vaccines.
Foot-and-Mouth Disease Virus/genetics* ; Virus Replication/genetics* ; Prolyl Oligopeptidases ; Serine Endopeptidases/physiology* ; Animals ; Cell Line ; RNA, Small Interfering/genetics* ; Foot-and-Mouth Disease/virology* ; Cricetinae

Objective To develop an erythrocyte-based delivery system for butyrylcholinesterase(BChE)that is capable of prophylaxis against organophosphorus nerve agents.Methods Recombinant BChE was produced and analyzed for oligomerization via polyacrylamide gel electrophoresis(PAGE)and Western blotting.A modified hypotonic preswelling method was employed to prepare BChE-loaded erythrocytes.The drug loading capacity and encapsulation efficiency were quantified using enzyme-linked immunosorbent assay(ELISA).Catalytic activity was assessed in vitro with an activity detection kit.The system was characterized via scanning electron microscopy(SEM),flow cytometry and a hematology analyzer.Results Recombinant BChE predominantly existed as dimers(85％dimer,15％monomer).The optimized volume ratio of erythrocytes to hypotonic solution was determined as 1:7.Compared with native and empty erythrocytes,BChE-loaded erythrocytes exhibited significantly higher catalytic activity(P＜0.001).The mean corpuscular volume of BChE-loaded erythrocytes increased(P＜0.001),while the mean content of corpuscular hemoglobin and hemoglobin in erythrocytes per 100 mL decreased(P＜0.001).SEM revealed no morphological differences(biconcave disc shape).Hypotonic preswelling moderately increased erythrocyte apoptosis(P＜0.001),but no statistical difference was observed between BChE-loaded and hypotonic-treated erythrocytes(P＞0.05).CD47 expression remained unchanged compared to native erythrocytes(P＞0.05).Conclusion The modified hypotonic preswelling method can generate BChE-loaded erythrocytes that retain the characteristics of native erythrocytes while conferring catalytic activity,offering a novel strategy for clinical intervention against organophosphorus poisoning.

Knee osteoarthritis is a common joint disease within osteoarthritis,characterized by pain,swelling,and limited functionality as the main clinical manifestations.In severe cases,it affects daily life and falls under the category of"impediment syndrome"or"bone impediment"in TCM.The author believes that the theory of"bones,tendons,and muscles"is closely related to this disease.Treatment should focus on simultaneously nourishing the liver,spleen and kidneys,considering tendons,bones and muscles,while also dispelling wind,cold and dampness.The clinical application of Sanbi Decoction has shown good efficacy,and this discussion aimed to provide ideas for the diagnosis and treatment of knee osteoarthritis.