ObjectivePolygoni Multiflori Radix is a commonly used tonic traditional Chinese medicine （TCM） in clinical practice， but liver injury has often been reported in recent years. Some related preparations containing Polygoni Multiflori Radix have been reported by the National Medical Products Administration many times for the risk of liver injury. This has caused extensive discussion on the potential toxicity of TCM in China and abroad， which has limited the clinical use of Polygoni Multiflori Radix to some extent. To understand the adverse reactions of Polygoni Multiflori Radix， the safe and rational use of Polygoni Multiflori Radix in clinical practice was discussed. MethodsThe pharmacovigilance thought of modern Chinese medicine and the TCM pharmacovigilance system framework of ''identification of poison， use of poison， anti-poison， and detoxification'' were employed to mine the relevant toxicity records， usage and dosage， processing compatibility， and contraindication of taking Polygoni Multiflori Radix in ancient books. The drug safety information of Polygoni Multiflori Radix was summarized by comparing with modern reports. ResultsA total of 74 ancient books related to Polygoni Multiflori Radix were included， suggesting that the toxicity of Polygoni Multiflori Radix was recognized in ancient times. The main chemical components of Polygoni Multiflori Radix had both efficacy and toxicity， and the adverse reactions may be related to long-term use， excessive use， and individual differences. The results showed that the toxic components of Polygoni Multiflori Radix could be reduced by peeling， steaming with black beans， and processing without iron tools. The toxic effects of Polygoni Multiflori Radix could be reduced by the compatibility of Polygoni Multiflori Radix with Poria， Psoraleae Fructus， and Cistanches Herba. ConclusionReasonable dosage， standard processing， correct compatibility， and syndrome differentiation are the key points to standardize the use of Polygoni Multiflori Radix and reduce the incidence of adverse reactions. Clinically， the toxicity classification of TCM should be strengthened， and the susceptible population should be prioritized. The detection indicators and early warning mechanisms should be improved， and precise drug dosage and course of treatment should be guaranteed. These measures can ensure the safe use of Polygoni Multiflori Radix.

ObjectivePolygoni Multiflori Radix is a commonly used tonic traditional Chinese medicine （TCM） in clinical practice， but liver injury has often been reported in recent years. Some related preparations containing Polygoni Multiflori Radix have been reported by the National Medical Products Administration many times for the risk of liver injury. This has caused extensive discussion on the potential toxicity of TCM in China and abroad， which has limited the clinical use of Polygoni Multiflori Radix to some extent. To understand the adverse reactions of Polygoni Multiflori Radix， the safe and rational use of Polygoni Multiflori Radix in clinical practice was discussed. MethodsThe pharmacovigilance thought of modern Chinese medicine and the TCM pharmacovigilance system framework of ''identification of poison， use of poison， anti-poison， and detoxification'' were employed to mine the relevant toxicity records， usage and dosage， processing compatibility， and contraindication of taking Polygoni Multiflori Radix in ancient books. The drug safety information of Polygoni Multiflori Radix was summarized by comparing with modern reports. ResultsA total of 74 ancient books related to Polygoni Multiflori Radix were included， suggesting that the toxicity of Polygoni Multiflori Radix was recognized in ancient times. The main chemical components of Polygoni Multiflori Radix had both efficacy and toxicity， and the adverse reactions may be related to long-term use， excessive use， and individual differences. The results showed that the toxic components of Polygoni Multiflori Radix could be reduced by peeling， steaming with black beans， and processing without iron tools. The toxic effects of Polygoni Multiflori Radix could be reduced by the compatibility of Polygoni Multiflori Radix with Poria， Psoraleae Fructus， and Cistanches Herba. ConclusionReasonable dosage， standard processing， correct compatibility， and syndrome differentiation are the key points to standardize the use of Polygoni Multiflori Radix and reduce the incidence of adverse reactions. Clinically， the toxicity classification of TCM should be strengthened， and the susceptible population should be prioritized. The detection indicators and early warning mechanisms should be improved， and precise drug dosage and course of treatment should be guaranteed. These measures can ensure the safe use of Polygoni Multiflori Radix.

ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

OBJECTIVE To provide a reference for anticoagulant therapy and vaginal bleeding management during medical abortion in patients with missed abortion after aortic mechanical valve replacement surgery. METHODS Clinical pharmacists conducted pharmaceutical monitoring on a patient with missed abortion after aortic mechanical valve replacement surgery， and analyzed the correlation between warfarin use and abortion. In response to gingival bleeding and an increase in the international normalized ratio （INR） after taking mifepristone， clinical pharmacists recommended discontinuing warfarin based on bleeding risk and INR changes； for the selection of sex hormones after missed abortion， clinical pharmacists suggested that estradiol gel combined with progesterone should be used in sequential treatment， supplemented by Xian yimucao capsules， to accelerate the elimination of residual tissue and congestion in uterine cavity. RESULTS The physician followed the advice of the clinical pharmacist and did not prolong the patient’s hospital stay due to excessive vaginal bleeding during treatment. Warfarin treatment was restarted on the day of discharge， and INR remained stable within the target anticoagulation range after discharge without any adverse events such as thromboembolism. CONCLUSIONS In patients with missed abortion after aortic valve replacement surgery， mifepristone may enhance the anticoagulant effect of warfarin and increase the risk of bleeding during medical abortion. It is recommended to discontinue warfarin before medication. Clinical pharmacists play a crucial role in the development of anticoagulation plans， identification of drug-drug interactions， assessment of bleeding risks， and selection of postoperative sex hormones. Through full pharmaceutical monitoring， they ensure the safety of patients’ medication.

ObjectiveTo investigate the novel post-translational modifications (PTMs) of SnRK2.6, a central component in the abscisic acid (ABA) signaling pathway, such as SUMOylation, and to establish a foundation for revealing the physiological functions and molecular mechanisms of SnRK2.6 regulated by these new modifications. MethodsThe interaction between SnRK2.6 and the SUMO E3 ligase SIZ1, as well as members of the SUMO protease family, was examined using yeast two-hybrid and in vitro pull-down assays. An in vitro SUMOylation system in Escherichia coli was utilized to determine whether SnRK2.6 undergoes SUMOylation. Mass spectrometry, combined with site-directed mutagenesis of candidate lysine residues, was employed to identify potential SUMOylation sites on SnRK2.6. In vitro de-SUMOylation assays were performed to assess whether SUMO proteases interacting with SnRK2.6 could catalyze the removal of SUMO moieties from modified SnRK2.6. The protein stability of SnRK2.6 was assessed in a cell-free degradation assay using bacterial-purified SnRK2.6 incubated with total protein extracts from Col and siz1 mutant seedlings. To dissect the genetic relationship between SnRK2.6 and SIZ1, stomatal aperture assays were performed under ABA treatment using snrk2.6, siz1, and snrk2.6 siz1 double mutant plants. ResultsSnRK2.6 physically interacts with SIZ1 and the SUMO protease ESD4, with the binding domains localized to the C-terminal region of SIZ1 and the N-terminal region of ESD4, respectively. SnRK2.6 was found to be SUMOylated, exhibiting two distinct high-molecular-mass bands ranging from 70 to 100 ku, indicative of modified forms. Bioinformatics analysis predicted four putative SUMOylation sites on lysine residues K57, K63, K142, and K190. Mass spectrometry identified three SUMOylation sites on K63, K142, and K174. However, individual or combinatorial point mutations on these sites had minimal impact on the pattern or intensity of SUMOylation signals, suggesting that these residues may not be responsible for the SUMOylation on SnRK2.6. Instead, such mutations only weaken the protein stability or accelerate the protein mobility of SnRK2.6. Therefore, the exact SUMOylation sites on SnRK2.6 remain unidentified. In de-SUMOylation experiments, incubation of GST-ESD4 with SUMOylated SnRK2.6 for 1-2 h led to the near-complete disappearance of both SUMOylated bands. In contrast, neither the GST control nor the catalytically inactive mutant GST-ESD4^C448S exhibited any de-SUMOylation activity. In protein turnover experiments, SnRK2.6 exhibited markedly enhanced half-life in siz1 compared with Col, indicating that SIZ1-dependent SUMOylation promotes SnRK2.6 turnover. Phenotypically, snrk2.6 mutants were completely insensitive to ABA-induced stomatal closure; siz1 mutants displayed pronounced hypersensitivity; and the snrk2.6 siz1 double mutant phenocopied snrk2.6—showing no significant response to ABA beyond that of the snrk2.6 mutant. These data indicate that SIZ1 acts as a negative regulator of ABA-triggered stomatal closure and SnRK2.6 functions as a positive regulator, and the inhibitory activity of SIZ1 is strictly dependent on SnRK2.6, placing SnRK2.6 genetically upstream of SIZ1 in the ABA signaling pathway. ConclusionSnRK2.6 undergoes SUMOylation, although the specific SUMOylation sites have not been defined. SnRK2.6 is dynamically regulated by reversible SUMOylation—catalyzed by SIZ1 and reversed by ESD4—which controls its protein stability. SUMOylation acts as a destabilizing signal for SnRK2.6, and SIZ1 exerts its negative effect on ABA-triggered stomatal closure probably through promoting SnRK2.6 degradation via SUMOylation. These findings uncover SUMOylation as a critical regulatory layer fine-tuning SnRK2.6 abundance in ABA signaling.

OBJECTIVE To provide a reference for anticoagulant therapy and vaginal bleeding management during medical abortion in patients with missed abortion after aortic mechanical valve replacement surgery. METHODS Clinical pharmacists conducted pharmaceutical monitoring on a patient with missed abortion after aortic mechanical valve replacement surgery， and analyzed the correlation between warfarin use and abortion. In response to gingival bleeding and an increase in the international normalized ratio （INR） after taking mifepristone， clinical pharmacists recommended discontinuing warfarin based on bleeding risk and INR changes； for the selection of sex hormones after missed abortion， clinical pharmacists suggested that estradiol gel combined with progesterone should be used in sequential treatment， supplemented by Xian yimucao capsules， to accelerate the elimination of residual tissue and congestion in uterine cavity. RESULTS The physician followed the advice of the clinical pharmacist and did not prolong the patient’s hospital stay due to excessive vaginal bleeding during treatment. Warfarin treatment was restarted on the day of discharge， and INR remained stable within the target anticoagulation range after discharge without any adverse events such as thromboembolism. CONCLUSIONS In patients with missed abortion after aortic valve replacement surgery， mifepristone may enhance the anticoagulant effect of warfarin and increase the risk of bleeding during medical abortion. It is recommended to discontinue warfarin before medication. Clinical pharmacists play a crucial role in the development of anticoagulation plans， identification of drug-drug interactions， assessment of bleeding risks， and selection of postoperative sex hormones. Through full pharmaceutical monitoring， they ensure the safety of patients’ medication.

Objective: To analyze the epidemiological characteristics of hand, foot and mouth disease (HFMD) among children aged 0-9 years in Guangzhou, so as to provide reference basis for further exploring scientifically effective prevention and control measures. Methods: Reported cases of HFMD in children aged 0-9 years in Guangzhou City from 2013-2025 were selected from China disease prevention and control information system, and the incidence in different years was analyzed descriptively; the trends of the composition ratio and incidence in various age groups were analyzed by using the Joinpoint regression model, spatial autocorrelation analyses were performed at the district level, and the seasonal autoregressive integrated moving average model (SARIMA) was applied to predict annual incidence rate for 2026. Results: From 2013 to 2025, the average annual reported incidence rate of HFMD among children aged 0-9 years in Guangzhou was 2 513.98/100 000, showing a fluctuating trend. Peaks of incidence occurred from May to July and from September to October. The male to female ratio was 1.49∶1. The average annual incidence rate was 4 743.99/100 000 in the 0-1 years age group, 3 298.19/100 000 in the 2-5 years age group, and 544.22/ 100 000 in the 6-9 years age group. Joinpoint regression analysis showed a decreasing trend in the proportion of the 0-1 years age group (APC= -6.02 %, t =-3.77) and an increasing trend in the proportion of the 6-9 years age group (APC=16.39%, t =5.67) (both P < 0.05 ). No significant global spatial clustering was observed at the district level; however, local scattered clusters were identified in certain areas. Using the SARIMA(2,0,0)(2,0,0) 12 model, the predicted annual incidence rate of HFMD among children aged 0-9 years in Guangzhou in 2026 was 2 680.56/100 000. Conclusions From 2013 to 2025, the annual incidence rate of HFMD among children aged 0-9 years in Guangzhou exhibited a fluctuating trend; the highest incidence rate is observed in the 0-1 years age group, while the proportion of cases in the 6-9 years age group increase year by year;and local spatial clusters of abnormal distribution are identified. It is essential to enhance risk monitoring and health education in key populations and areas to mitigate the risk of infection in children.

Objective:This study aimed to integrate RNA-seq data to identify key genes associated with macrophage-ferroptosis and develop a prognostic model for hepatocellular carcinoma(HCC).Methods:We retrieved a dataset from the GEO database containing transcriptome data and clinical information for 163 samples.Macrophage-related genes were identified using WGCNA and immune infiltration analyses.Ferroptosis-related genes from the FerrDbV2 database were intersected with differentially expressed genes to obtain significant macrophage-ferroptosis-related genes.Hub genes were screened via protein interaction network construction,and key genes were identified using four machine learning algorithms.These genes exhibited significant expression differences between cancer and normal tissues and were closely linked to patient prognosis.ROC curve and KM survival analyses were performed,and expression levels were validated at the transcriptome and proteome levels.Results:Four key genes RRM2,KIF20A,PCK2,and PDK4 were identified and evaluated.RRM2 and KIF20A demonstrated high importance in classification prediction models and reliable performance in ROC and KM analyses(AUC＞0.9,P＜0.05).These genes regulate cancer cell proliferation/survival and macrophage polarization/function,influencing the tumor microenvironment and HCC progression.Conclusion:RRM2 and KIF20A regulate cancer cell proliferation and survival,modulate macrophage polarization and function,and influence the immune response in the tumor microenvironment.They can serve as prognostic biomarkers and potential immunotherapy targets for hepatocellular carcinoma.

Sampling is the first stage of the DNA Typing in forensic science,and some studies found that the sampling technology affected the outcomes of"Contact DNA"testing.Since swabs are the most commonly used collection instrument for"Contact DNA",the researchers in forensic science field should pay more attention to study the collection efficiency of swabs.However,currently the majority of relevant research is focused on downstream testing processes,such as typing and amplification;the corresponding work on sampling performance by swabs is quite limited.Furthermore,the absence of an internationally recognized standard procedure makes it impossible to directly compare the collection results among laboratories.In this paper,a review on the use of swabs in the forensic science field is presented.It analyzes the collection efficiency,advantages and disadvantages of different swabs,and investigates the need and feasibility of developing a standardized method to evaluate the swab collection efficiency,for improving the sampling performance of swabs and ultimately increasing the detection rate of"Contact DNA"in forensic science.

AIM To investigate the impact of varying dosages of Supplemented Wendan Decoction on the PI3K/Akt/FOXO1 glycolipid metabolic pathway in 3T3-L1 adipocytes.METHODS The CCK-8 assay was used to determine the concentration of Supplemented Wendan Decoction-medicated serum.The mature adipocytes differentiated from 3T3-L1 preadipocytes after induction were further divided into the blank control group,the model group,the rosiglitazone group(10 mg/L),and the Supplemented Wendan Decoction groups(5％,10％,and 20％),followed by the sample collections after 48 hours of treatment.Oil red O staining quantified lipid accumulation in 3T3-L1 adipocytes;extracellular glucose levels were measured using glucose oxidase(GOD)assay;RT-qPCR analyzed mRNA expressions of IRS-1,PI3K,Akt,GLUT4,IL-6,TNF-α and IL-1β;Western blot assessed protein expressions of INSR,IRS-1,PI3K-p85,Akt,FOXO1 and GLUT4.RESULTS No significant changes in cell viability(P＞0.05)were observed in 3T3-L1 preadipocytes exposed to serum containing supplemented Wendan Decoction at different concentrations for 24,48,or 72 hours.The 3T3-L1 preadipocytes held the capacity to differentiate into mature adipocytes within a 14-day induction period.Compared to the model group,all supplemented Wendan Decoction groups exhibited reduced lipid accumulation in adipocytes and downregulated mRNA expression of IRS-1,IL-6,TNF-α and IL-1β(P＜0.01);the low-dose group demonstrated increased mRNA expressions of PI3K and GLUT4(P＜0.05,P＜0.01),alongside elevated protein expressions of INSR,IRS-1,PI3K-p85,Akt and GLUT4(P＜0.05,P＜0.01);the medium-dose group showed enhanced GLUT4 mRNA expression,and upregulated protein expressions of INSR and FOXO1(P＜0.01).After 24 hours intervention,the high-dose Supplemented Wendan Decoction group exhibited increased glucose consumption in adipocytes(P＜0.01),and elevated protein expression of INSR,Akt and FOXO1(P＜0.05,P＜0.01).CONCLUSION Supplemented Wendan Decoction reduces lipid accumulation in adipocytes,regulates glucose and lipid metabolism,and promotes metabolic homeostasis through PI3K/Akt/FOXO1 signaling pathway.