OBJECTIVE To investigate a dynamic monitoring of drug consumption （DMDC） model based on the seasonal Mann-Kendall trend test， aiming to provide scientific evidence for the efficient and macroscopic monitoring of drug use. METHODS A monitoring list of key outpatient drugs was established based on the top 20% of drugs ranked by sales volume in the outpatient pharmacy in October 2024. A DMDC model based on the Mann-Kendall trend test was constructed using the monthly usage data of key outpatient drugs from November 2021 to October 2024， aiming to eliminate the impact of seasonal fluctuations and analyze the temporal trends in drug consumption. Taking mucolytic expectorants， triazole derivatives for dermatophytosis， and single-agent hydroxymethylglutaryl coenzyme A （HMG-CoA） reductase inhibitors as examples， the monitoring effectiveness of the DMDC model was demonstrated， and its performance was compared with that achieved by the traditional sequential growth rate ranking method. RESULTS A total of 215 drug varieties were included in the monitoring list， and DMDC models were successfully established for all of them. Among these， 119 showed a significant increasing trend （P＜0.05， S′＞0）. The model successfully monitored the monthly consumption of mucolytic expectorants， triazole derivatives for dermatophytosis， and single- agent HMG-CoA reductase inhibitors. The precision and recall rates of the DMDC model for identifying abnormal drug use were 60.7% and 85.0%， respectively， both significantly higher than those of the sequential growth rate ranking method （8.3% and 15.0%， respectively） （χ2＝20.114， P＜0.001； χ2＝19.600， P＜0.001）. CONCLUSIONS DMDC model based on the seasonal Mann-Kendall trend test can effectively identify long-term trends in drug consumption， eliminate seasonal interference， enhance monitoring accuracy and management efficiency， and is suitable for the dynamic monitoring of drug consumption.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

AIM: To investigate the differences in morphological structure and retinal blood perfusion between the affected eye and the contralateral healthy eye using optical coherence tomography angiography(OCTA)in patients with idiopathic macular epiretinal membrane(IMEM)before and after surgery, and to evaluate the association of these parameters with functional and anatomical outcomes to inform prognostic assessment. METHODS:A prospective study was conducted at Zhejiang Provincial People's Hospital between January 2023 and December 2024. Consecutive patients diagnosed with unilateral IMEM were enrolled; the fellow eye served as an internal control. All participants underwent standardized ophthalmic evaluations, including optical coherence tomography(OCT), OCTA, and color fundus photography. Key quantitative parameters assessed included best-corrected visual acuity(BCVA), central macular thickness(CMT), foveal avascular zone(FAZ)area, vessel density in the inner capillary plexus(ICP), superficial capillary plexus(SCP), deep capillary plexus(DCP), and choroidal capillary perfusion area(CCPA). Measurements were obtained preoperatively and at 1 and 3 mo postoperatively. Correlation analyses were performed between the above parameters and postoperative BCVA and CMT.RESULTS: This study enrolled 30 patients(60 eyes)diagnosed with IMEM, comprising 14 males and 16 females, with a mean age of 65.4±10.8 y.At baseline, IMEM-affected eyes demonstrated significantly reduced BCVA, DCP density, and FAZ area, alongside significantly increased CMT and CCPA, compared with contralateral controls. Following vitrectomy with membrane peeling, CMT decreased significantly at both 1 and 3 mo(both P<0.05)postoperatively; DCP density and BCVA showed significant improvement(both P<0.05). No significant change in FAZ area was observed postoperatively(P>0.05). At 3 mo postoperatively, BCVA of the affected eye was negatively correlated with CMT(r=-0.549, P=0.022). At 1 mo postoperatively, CMT was negatively correlated with preoperative DCP and FAZ, positively correlated with preoperative CMT, and positively correlated with ICP and SCP at 1 mo postoperatively, and negatively correlated with FAZ at 1 mo postoperatively(all P<0.05). Furthermore, CMT at 3 mo postoperatively was negatively correlated with preoperative DCP(r=-0.498,P=0.042).CONCLUSION:In patients with IMEM, the affected eyes exhibit significantly reduced DCP density and FAZ area, alongside increased CMT and CCPA. Following vitrectomy with membrane peeling, CMT decreased progressively, DCP density demonstrated partial restoration, and vision improved gradually. Preoperatively, smaller CMT larger DCP, and FAZ were associated with more favorable surgical outcomes; postoperatively, smaller ICP and SCP densities—combined with a larger FAZ—also correlated with better functional recovery.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

Objective : To investigate the diagnostic value of plasma calprotectin in childern with refractory mycoplasma pneumoniae pneumonia(RMPP). Methods : A multicenter, prospective cohort study was conducted, enrolling 228 children with mycoplasma pneumoniae pneumonia(MPP). Among these, 177 cases were diagnosed with general mycoplasma pneumoniae pneumonia(GMPP), while the remaining 51 cases were RMPP. Plasma was collected at the time of admission of the children in both groups, and calprotectin levels were measured. A one-way difference analysis was performed on the blood test indexes of the children in the two groups, and the difference variables withP<0.05 between the two groups were included in a multifactorial logistic regression to analyze the risk factors for the progression of GMPP to RMPP. The differential diagnostic value of plasma calprotectin for GMPP and RMPP was analyzed by the receiver operating characteristic(ROC) curves. Results : Univariate analysis showed that plasma calprotectin levels were significantly higher in the RMPP group than those in the GMPP group, and the difference was statistically significant(P<0.05). Logistic regression analysis showed that plasma calprotectin was an independent risk factor for RMPP(OR=1.323,P<0.001), ROC curve analysis showed that plasma calprotectin had a higher diagnostic value for the differential diagnosis of GMPP and RMPP(AUC =0.839), and its combination with C-reactive protein and albumin could significantly improve the diagnostic efficiency. Conclusion Plasma calprotectin has good clinical value for the diagnosis of RMPP.

The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer's disease (AD) research. Here, we present PI4AD, a computational medicine framework that integrates multi-omics data, systems biology, and artificial neural networks for therapeutic discovery. This framework leverages multi-omic and network evidence to deliver three core functionalities: clinical target prioritisation; self-organising prioritisation map construction, distinguishing AD-specific targets from those linked to neuropsychiatric disorders; and pathway crosstalk-informed therapeutic discovery. PI4AD successfully recovers clinically validated targets like APP and ESR1, confirming its prioritisation efficacy. Its artificial neural network component identifies disease-specific molecular signatures, while pathway crosstalk analysis reveals critical nodal genes (e.g., HRAS and MAPK1), drug repurposing candidates, and clinically relevant network modules. By validating targets, elucidating disease-specific therapeutic potentials, and exploring crosstalk mechanisms, PI4AD bridges genetic insights with pathway-level biology, establishing a systems genetics foundation for rational therapeutic development. Importantly, its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation-provides a strategy to disrupt AD progression, complementing conventional amyloid/tau-focused paradigms, with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.

The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.

Objective To analyze the factors influencing the mobilization and collection of peripheral blood hematopoietic stem cells in patients with hematologic tumors,and to explore the predictive value of platelet counts in the process of autologous stem cell collection.Methods A total of 52 patients with hematologic tumors who underwent autologous hematopoietic stem cell transplantation in Affiliated Jinhua Hospital,Zhejiang University School of Medicine from September 2018 to March 2024 were selected.Binary Logistic regression analysis was used to explore the influencing factors of peripheral blood stem cell collection,and receiver operating characteristic(ROC)curve was used to determine the optimal cut-off value of platelet counts before collection.Results Among the 52 patients,36 patients had high-quality mobilization and 16 patients had non-high-quality mobilization.The number of chemotherapy cycles before collection and mobilization plan had significant effects on the number of CD34+cells collected,while age,gender,collection machine,and bone marrow involvement had no significant effects on the number of CD34+cells collected.The platelet counts in high-quality mobilization group were significantly higher than those in non-high-quality mobilization group(P＜0.05).Binary Logistic regression analysis showed that platelet counts before collection had a significant effect on the collection of peripheral blood stem cells(OR=0.975,95％CI:0.954-0.997,P=0.025).ROC curve results showed that the area under the curve of platelet counts prediction of stem cell quality collection was 0.732,the optimal cut-off value was 86×109/L,the sensitivity was 72.2％,and the specificity was 81.2％.Subgroup analysis showed that platelet transfusion had no significant effect on the number of CD34+cells.Conclusion The number of chemotherapy cycles before collection and mobilization plan can affect the number of autologous hematopoietic stem cells.The platelet counts before collection can help determine the best time for collection and improve the success rate of collection.

Objective To observe the value of spectral CT material separation technology for diagnosing traumatic bone marrow edema in limbs.Methods Totally 51 patients with limb traumatic bone marrow edema were retrospectively enrolled and divided into young group(n=26,18-43 years)and middle-aged group(n=25,46-74 years).Taken MRI as reference standard,the efficacy of spectral CT Water-hydroxyapatite(HAP)image for diagnosing bone marrow edema in trauma area was analyzed,and the Water-HAP density values were compared between groups.Results No significant difference of diagnosing bone marrow edema was found between spectral CT and MRI(x2=0.201,P=0.654),and the consistency was high(Kappa=0.774).Water-HAP density value in bone marrow edema area was higher than that in non bone marrow edema area(t=24.634,P＜0.05),and no significant difference of Water-HAP density values in bone marrow edema area nor non bone marrow edema area was found between young group and middle-aged group(both P＞0.05).Conclusion Spectral CT material separation technology was helpful for diagnosing traumatic bone marrow edema in limbs.

[Purpose]To analyze global epidemic status of colorectal cancer and explore the rela-tionship between the human development index(HDI)and the burden of colorectal cancer.[Methods]Based on the GLOBOCAN 2022 estimation data,the disease burden of colorectal can-cer in different regions,countries,and levels of HDI were analyzed.Spearman's rank test was used to explore the correlation between HDI and colorectal cancer disease burden.[Results]The estimated global incidence of colorectal cancer in 2022 was 1 926 425 cases(1 069 446 for male and 856 979 for female),with a age-standardized incidence rate of 18.4/105(21.9/105 for male and 15.2/105 for female),and cumulative risk of incidence of 2.10％(2.60％for male and 1.70％for female);the estimated number of deaths was 904 019(499 775 for male and 404 244 for fe-male),with a age-standardized mortality rate of 8.1/105(9.9/105 for male and 6.5/105 for female)and cumulative risk of death of 0.84％(1.00％for male and 0.65％for female).1-crude mortality rate/crude incidence rate(1-M/I)was 0.53(0.53 for male and 0.53 for female).Large disparities were in the disease burden of colorectal cancer between different regions and countries.After grouped by HDI,we found that the age-standardized incidence rates in very high,high,median,and low HDI regions were 28.6/105,18.1/105,6.7/105,and 6.4/105,and the standardized mortality rates were 10.5/105,8.3/105,3.9/105,and 4.5/105,with 1-M/I of 0.57,0.52,0.43 and 0.30,respec-tively;and the incidence and mortality rates were increasing with age.Spearman's correlation analysis showed a strong positive correlation between HDI and colorectal cancer in age-standardized incidence(r=0.84),age-standardized mortality(r=0.71)and 1-M/I(r=0.82)(all P＜0.001).[Con-clusion]The global burden of colorectal cancer remains high.There are disparities in the disease burden among countries and regions,which is positively correlated with their HDI levels,indicating that the colorectal cancer prevention and treatment strategies should be developed based on the conditions of each regions and countries accordingly.