The Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines （hereinafter referred to as the Guidelines） is first specialized in the field of drug safety for oral Chinese patent medicines （OCPMs） in China. Rooted in China's healthcare context， the Guidelines address the unique usage patterns and risk characteristics of OCPMs， filling a regulatory gap in the pharmacovigilance framework specific to this category. To facilitate accurate understanding and effective implementation of the Guidelines， and to promote the standardized development of pharmacovigilance practices for OCPMs， this study offered a systematic interpretation based on its three core components. In the domain of risk monitoring and reporting， the paper analyzed the rationale for multi-source information integration and clarified the criteria for identifying key products and target populations for intensive monitoring. Regarding risk assessment， the Guidelines were examined from three dimensions of formulation components， medication behaviors， and population to address complex safety issues arising from medicinal constituents， irrational use， and individual susceptibility. In the area of risk control， the analysis focused on context-based interventions and dynamic closed-loop management strategies， exploring practical pathways to shift from passive response to proactive risk mitigation. Furthermore， this paper evaluated the applied value of the Guidelines and identified implementation challenges， such as insufficient capacity at the primary-care level and limited digital infrastructure. In response， the study proposed optimization strategies including establishing a dynamic updating mechanism， strengthening training at the grassroots level， and incorporating artificial intelligence to enhance pharmacovigilance capacity. This interpretation aims to provide actionable insights for marketing authorization holders （including manufacturers）， pharmaceutical distributors， healthcare institutions， and research organizations， ultimately supporting the establishment and refinement of a full lifecycle pharmacovigilance system for OCPMs.

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.

ObjectiveThe exacerbating trend of global population aging poses profound socioeconomic and public health challenges, making the comprehensive elucidation of biological aging mechanisms and the discovery of effective anti-aging interventions an urgent priority in the life sciences. Based on our previous serum metabolomics findings that dimethylglycine, an intermediate metabolite of amino acid metabolism naturally present in the human body, was significantly enriched in the serum of longevity families, this study aimed to systematically investigate the anti-aging effects of dimethylglycine both in living organisms and in controlled laboratory environments, and to preliminarily elucidate its underlying molecular mechanisms. While existing literature indicates that dimethylglycine possesses antioxidant and immunomodulatory properties, its direct anti-aging efficacy and the specific molecular pathways through which it operates remain largely unexplored. MethodsTo comprehensively evaluate the anti-aging properties of dimethylglycine, we utilized replicative senescent human embryonic lung fibroblasts, specifically the WI-38 cell line, as an experimental model in a controlled laboratory environment. Cell viability and safety were thoroughly assessed using Cell Counting Kit-8 and lactate dehydrogenase release assays across various concentrations of dimethylglycine. The impact of dimethylglycine on cellular senescence phenotypes, oxidative stress, and proliferative capacity was evaluated via senescence-associated beta-galactosidase staining, reactive oxygen species fluorescence detection, and 5-ethynyl-2'-deoxyuridine incorporation assays. Furthermore, the molecular alterations of senescence-associated secretory phenotype factors and core senescence signaling pathways were quantified using quantitative reverse transcription polymerase chain reaction for the messenger RNA levels of interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1, and enzyme-linked immunosorbent assay for the measurement of p16 and p21 protein expression levels. For the living organism model, the wild-type nematode Caenorhabditis elegans was used to evaluate systemic physiological effects. We conducted a comprehensive lifespan analysis at 20°C, heat stress resistance survival assays at 35℃, senescence-associated beta-galactosidase staining, lipofuscin accumulation tracking, intracellular reactive oxygen species measurement, and Oil Red O staining to ascertain systemic lipid accumulation. Additionally, network pharmacology bioinformatics tools, including PharmMapper and STRING databases, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were utilized to predict target pathways, alongside highly detailed molecular docking simulations utilizing SwissDock and Protein-Ligand Interaction Profiler to examine interactions with the cytochrome P450 family 2 subfamily C member 9 protein. ResultsThe experimental outcomes robustly demonstrate the potent anti-aging capabilities of dimethylglycine. At the cellular level, toxicity analyses firmly confirmed that dimethylglycine is highly safe; continuous treatment with 50 mol/L and 70 mol/L of dimethylglycine for 5 d did not induce any cellular membrane damage or cytotoxicity, but rather actively promoted cellular proliferation. Utilizing the optimal standardized concentration of 50 mol/L, dimethylglycine treatment significantly ameliorated senescent phenotypic markers in human embryonic lung fibroblasts, which was evidenced by a drastic and highly significant reduction in the senescence-associated beta-galactosidase positive cell percentage (P<0.000 1) and intracellular reactive oxygen species levels (P<0.000 1), alongside a marked increase in the 5-ethynyl-2'-deoxyuridine-positive proliferation rate (P=0.003 5). On a molecular expression scale, dimethylglycine significantly downregulated the messenger RNA expression of multiple core senescence-associated secretory phenotype inflammatory factors, including interleukin-6, interleukin-8, p21, and matrix metalloproteinase-1. Concurrently, it effectively suppressed the protein expression of critical cell cycle arrest markers, diminishing p16 protein levels by 57.3% (P=0.000 4) and p21 protein levels by 27.2% (P=0.000 7). In the nematode Caenorhabditis elegans animal model, dimethylglycine significantly extended the mean lifespan from 20.402 d to an impressive 23.066 d (P<0.000 1) and notably enhanced overall survival rates under severe heat stress environmental conditions (P=0.017). Furthermore, systemic dimethylglycine intervention significantly mitigated age-related physiological decline by decreasing bodily lipofuscin accumulation (P<0.000 1), significantly reducing senescence-associated beta-galactosidase activity, lowering systemic reactive oxygen species fluorescence (P=0.008), and effectively alleviating overall fat accumulation (P<0.000 1). Mechanistically, extensive network pharmacology and Kyoto Encyclopedia of Genes and Genomes analyses strongly revealed that the potential targets of dimethylglycine are significantly enriched in fundamental drug metabolism and oxidative stress response pathways. Precision molecular docking simulations conclusively demonstrated that dimethylglycine forms highly stable structural interactions with the cytochrome P450 family 2 subfamily C member 9 protein, specifically highlighting the definitive formation of 5 stable hydrogen bonds involving serine 365, leucine 366, and serine 429 residues, as well as two critical salt bridge formations with arginine 97 and histidine 368 residues. It is additionally predicted to interact favorably with glutathione S-transferase family proteins. ConclusionDimethylglycine exhibits a profoundly significant and multifaceted anti-aging activity at both the cellular and entire living animal levels. By powerfully alleviating oxidative stress, heavily suppressing the core p16 and p21-dependent cellular senescence signaling pathways, and substantially mitigating the detrimental senescence-associated secretory phenotype, dimethylglycine effectively delays fundamental cellular senescence processes and drastically extends whole-organism lifespan. The biological mechanisms driving these robust protective effects are highly likely closely associated with its direct stable interactions with crucial metabolic and detoxifying enzyme systems, such as cytochrome P450 family 2 subfamily C member 9 and glutathione S-transferase family proteins, thereby systemically improving metabolic dysregulation and restoring critical redox homeostasis. This comprehensive study provides highly solid experimental evidence supporting dimethylglycine as a highly potent and safe potential anti-aging intervention agent, while simultaneously offering a clear molecular mechanistic explanation for the previously documented high abundance of dimethylglycine observed within exceptionally long-lived human populations.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

Objective To construct a dynamic prediction model for JC polyomavirus (JCV) reactivation after kidney transplantation. Methods A retrospective analysis was conducted on the clinical data of 128 recipients who met the inclusion criteria and received kidney transplantation in Nanfang Hospital, Southern Medical University, from June 2021 to December 2024. Dynamic Cox regression and dynamic restricted mean survival time (RMST) regression based on the landmark method were adopted to establish the dynamic prediction models, and Monte Carlo cross-validation was used to evaluate model performance. Results The dynamic models could predict the incidence and onset time of JCV reactivation within the subsequent 3 months according to covariates at each landmark time point from the 1st to the 6th month after transplantation. Remuzzi score, body mass index and warm ischemia time were independent risk factors for JCV reactivation, while a history of urinary BK polyomavirus reactivation served as a protective factor. The median values of the area under the curve, C-index and Brier score of the dynamic Cox model were 0.873, 0.851 and 0.065 respectively, and the C-index of the dynamic RMST model was 0.829, all of which were superior to those of the static model. Conclusions The landmark-based dynamic models exhibit excellent predictive performance, which may integrate baseline data and post-transplant follow-up information to realize dynamic assessment of the risk and time window of JCV reactivation, thereby providing evidence for optimizing post-operative monitoring and individualized intervention strategies.

Dry eye disease(DED)is a multifactorial ocular surface disorder characterized by the loss of tear film homeostasis among which evaporative DED associated with meibomian gland dysfunction(MGD)accounts for up to 86%, and traditional drugs fail to effectively target the core pathological mechanism. As a new type of anhydrous and preservative-free eye drops approved by the FDA, perfluorohexyloctane has a unique amphiphilic structure, which can form an artificial lipid monolayer at the air-liquid interface of the tear film. It exerts its therapeutic effects by inhibiting tear evaporation, stabilizing the tear film, unclogging meibomian gland orifices, and promoting corneal oxygen supply. This drug can not only serve as a first-line treatment option for evaporative DED but also be combined with other drugs for personalized treatment. This review summarizes the mechanism of action, pharmacological properties, clinical efficacy, and safety of perfluorohexyloctane eye drops, and further elaborate on its application value in complex types of DED and patients with other concurrent ocular surface diseases, aiming to provide more evidence support for the precise treatment of DED.

Objective: To analyze the demographic evolution of China over the forthcoming decade (2026-2035) and to systematically evaluate its potential implications for voluntary blood donation practices and the equilibrium of clinical blood supply and demand. Methods: Leveraging comprehensive blood collection and utilization data from 2021 to 2025 at the national, provincial (Shandong), and municipal (Zibo) levels, we identified and examined critical determinants influencing blood management systems. The DeepSeek-V3.2 large language model was deployed to project future population age structures, and to generate quantitative estimates for hospitalization volumes, clinical blood requirements, available blood supply, and donation frequencies for the target years 2030 and 2035, thereby furnishing an evidence base for strategic planning and priority-setting. Results: DeepSeek-derived projections indicate that the proportion of China's population aged 60 years and above will surpass 27% (370 million/1 380 million) by 2030 and exceed 30% (400 million/1 350 million) by 2035, signaling a marked acceleration in population aging. This demographic shift is projected to reduce the proportion of the national population eligible to donate blood from 59.2% (835 million out of 1.41 billion) to 52% (710 million out of 1.36 billion), while the demand for blood is expected to increase by 87.8% relative to 2024, rising from 26.927 million units to 50.56 million units. Sustaining blood supply-demand balance will necessitate progressive annual increases in donation rates. Under prevailing policy frameworks, the required blood donation rate among the eligible population in Shandong Province would need to rise by 122.57% by 2035 [from 20.07‰ (1.1641 million person-times/58 million people) to 44.67‰ (2.189 million person-times/49 million people)] to potentially satisfy projected clinical requirements. Conclusion: By integrating DeepSeek-V3.2, AI predictive models, and blood donation incentive measures, it is possible to monitor population demographics, forecast clinical blood demand, manage blood supplies, and ensure the long-term sustainability of clinical blood availability. It must be acknowledged, however, that the present analysis is constrained by a limited data foundation (comprising only five annual observation points); accordingly, the projections should be interpreted as directional trend indicators or methodological illustrations rather than definitive quantitative forecasts.

Objective:To investigate the predictive value of pre-infarction angina(PIA)combined with serum lipo-protein-associated phospholipase A2(Lp-PLA2)for no-reflow during primary percutaneous coronary interven-tion(PCI)in elderly patients with new-onset acute ST-segment elevation myocardial infarction(STEMI).Meth-ods:A total of 189 patients who hospitalized because of acute STEMI and underwent primary PCI within 12h in De-partment of Cardiology,Cangzhou People's Hospital between January 2018 and December 2022 were enrolled.Ac-cording to their TIMI blood flow during PCI,the patients were divided into no reflow group(n=42)and normal re-flow group(n=147).The baseline data were compared between two groups.Multivariate Logistic regression analy-sis was used to analyze the risk factors of no-reflow during PCI.The receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of PIA and Lp-PLA2 for no-reflow.Results:PI A occurred in 73 cases(38.6％),and no reflow occurred in 42 cases(22.2％)during primary PCI.Compared with patients in normal re-flow group,those in no reflow group had significant higher Lp-PLA2[(341.33±98.32)ng/ml vs.(261.95±75.21)ng/ml]and onset to reperfusion time[(7.02±1.28)h vs.(5.14±1.48)h],and significant lower incidence of PIA(23.8％ vs.42.9％)(P＜0.05 or＜0.01).Multivariate Logistic regression analysis showed that Lp-PLA2(OR=1.528,95％CI 1.028～2.030,P＜0.001),onset to reperfusion time(OR=2.602,95％CI 1.848～3.665,P＜0.001)were independent risk factors for no reflow during PCI in elderly STEMI patients,while PIA was an inde-pendent protective factor(OR=0.261,95％CI 0.101～0.671,P=0.005).The area under ROC curve of Lp-PLA2 combined PIA was 0.863(95％CI 0.806～0.909),which was significantly higher than those of Lp-PLA2[0.733(95％CI 0.664～0.794),Z=2.690,P=0.007]and PIA alone[0.609(95％CI 0.535～0.679),Z=5.657,P＜0.001].Conclusion:Pre-infarction angina has an important protective effect on no-reflow in STEMI patients.High Lp-PLA2 and absence of pre-infarction angina at admission may be good predictors of no-reflow during primary PCI in elderly patients with newly-onset acute STEMI,and it contributes to risk stratification of high risk patients.

Objective:To investigate the glymphatic system dysfunction and white matter microstructural damage in type 2 diabetic mellitus patients with diabetic peripheral neuropathy (DPN), and to identify the early diagnostic imaging biomarkers.Methods:Thirty-one DPN patients and 31 type 2 diabetes mellitus (T2DM) patients who attended the First People's Hospital of Yancheng from March 2022 to October 2023 were included. In addition, 40 healthy controls (HC) were recruited. All subjects underwent 3.0T MRI scan with diffusion tensor imaging and 3D-T1WI sequences, and the diffusion tensor imaging analysis along the perivascular space(DTI-ALPS) index, perivascular space volume fraction in white matter(PVSVF-WM) and peak width of skeletonized mean diffusivity (PSMD) were calculated. SPSS 26.0 software was used to perform one-way ANOVA, t-tests, and Chi-square tests to compare clinical data and imaging indicators among the three groups. Partial correlation analysis was used to explore the relationships between DTI-ALPS index, PVSVF-WM, PSMD and clinical indicators in DPN patients. Finally, receiver operating characteristic (ROC) curves were plotted to evaluate the diagnostic value of DTI-ALPS index, PVSVF-WM, and PSMD for DPN. Results:The DPN group(1.46±0.19)had considerably lower DTI-ALPS index than the T2DM group (1.59±0.14) and HC group (1.60±0.17) (both P<0.05, Bonferroni correction). The DPN group (1.44±0.11) had significantly higher PVSVF-WM than both the T2DM group (1.35±0.14) and HC group (1.26±0.13) (both P<0.05, Bonferroni correction). The DPN group (1.84±0.31) and the T2DM group (1.83±0.25) had higher PSMD than HC group (1.60±0.24) (both P<0.05, Bonferroni correction), but the difference between the DPN group and the T2DM group was not statistically significant ( P>0.05). The DTI-ALPS index in the DPN group were negatively correlated with PSMD ( r=-0.379, P=0.035). The DTI-ALPS index was negatively correlated with the Toronto clinical scoring system (TCSS) score ( r=-0.456, P=0.01), while PSMD was positively correlated with TCSS scores ( r=0.686, P<0.001) in DPN group. The ROC curves showed that the area under the curve (AUC) was 0.777 ( P<0.001) for the combined diagnosis of DPN with the DTI-ALPS index, PVSVF-WM and PSMD. Conclusion:DPN patients exhibit glymphatic system dysfunction and white matter microstructural damage. The DTI-ALPS index and PSMD can serve as objective markers for assessing DPN severity. The combination of glymphatic system function indicators and white matter microstructural damage markers has moderate diagnostic value for peripheral neuropathy in T2DM patients.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.