BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

BACKGROUND:Age-related macular degeneration and deep vein thrombosis may share common pathophysiological mechanisms,but there is a lack of direct evidence regarding their relationship.Traditional studies are confounded by confounding factors and reverse causation.OBJECTIVE:To investigate the causal relationship between age-related macular degeneration and deep vein thrombosis based on Mendelian randomization design.METHODS:Through a two-way Mendelian randomization analysis,single nucleotide polymorphisms of exposure and outcomes were obtained from publicly available genome-wide association studies,with deep vein thrombosis data from the FinnGen database in a European population with a sample size of 363 612 and 1 048 575 single nucleotide polymorphisms.In addition,we obtained data on age-related macular degeneration from the IEUOpenGWAS project,also from a European population sample of 105 248 cases covering 11 304 110 single nucleotide polymorphisms.In R4.4.1,we used the TwoSampleMR package(version 0.6.8)to explore the causal effects of exposure factors on outcomes.At the same time,we also conducted a sensitivity analysis via MR-Egger regression,weighted median,weighted model and simple model methods to ensure that the assessment results were robust and reliable.In addition,we used the"heterogeneity"function to test for heterogeneity,and the"horizontal pleiotropy"function and the MR-PRESSO test to further assess horizontal pleotropy.The Cochran's Q test was used to determine whether there was statistical heterogeneity between single nucleotide polymorphisms,and the leave-one-out method was used to assess whether single nucleotide polymorphisms would significantly interfere with Mendelian randomization analysis.Funnel plots were drawn to assess the potential bias of single nucleotide polymorphisms.Forest plots were plotted to show the effect estimates of single nucleotide polymorphisms on exposure and outcomes,and their confidence intervals were plotted.Scatter plots were plotted to evaluate the relationship between the potency of single nucleotide polymorphisms and their causal effect size on outcome estimates.RESULTS AND CONCLUSION:Both forward and reverse studies showed that there was no causal association between age-related macular degeneration and the occurrence of deep vein thrombosis(P＞0.05).Sensitivity analysis showed that the main analysis results were reliable and robust,with no outliers,heterogeneity,and horizontal pleiotropy,and no single nucleotide polymorphism significantly affected the overall effect estimate.Although it is based on European population data,it has methodological reference value for Chinese biomedical research on complex disease associations.In this field,China can carry out multi-center large-sample studies,accurately analyze the internal links between Chinese population-related diseases,and provide a basis for prevention and treatment strategies and clinical practice.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

ObjectiveBased on the regulation of macrophage M2 polarization， this study aims to explore the molecular mechanism and action targets of the Qijia Rougan prescription and its key effector ingredients in anti-fibrosis， thereby providing a basis and reference for the development of new drugs for hepatic fibrosis. MethodsA rat model of hepatic fibrosis was established by subcutaneous injection of 40%CCl₄， followed by oral administration of Qijia Rougan granules. The volume of collagen fibers was detected using Masson staining， the fibrosis markers Collagen Ⅰ and α-SMA were detected using immunohistochemistry， the proportion of M2 macrophages was detected by flow cytometry. The expression levels of M2 macrophage phenotype markers CD163 and CD206 were detected using immunofluorescence double staining. Western blot was used to detect the levels of the transforming growth factor-β （TGF-β）， platelet derived growth factor subunit B （PDGFB）， interleukin-10 （IL-10）， phosphorylated Janus kinase 1 （p-JAK1）， and phosphorylated signal transducer and activator of transcription 6 （p-STAT6）. Real-time fluorescent quantitative PCR was used to detect the relative expression levels of JAK1， STAT6， Arginase 1（Arg1）， and Fizz1. Based on the theory of serum pharmacology， liquid chromatography-mass spectrometry and WENN analysis were used to obtain the active ingredients of Qijia Rougan prescription. Molecular docking and molecular dynamics simulation were performed to analyze the effector ingredients and their targets. The identified effector ingredients were interfered with IL-4-induced M2 polarization of RAW264.7 macrophage in vitro to validate the targets. ResultsQijia Rougan prescription significantly reduced the content of fibrosis markers α-SMA and Collagen Ⅰ， as well as collagen fiber content （P<0.05）. It decreased the proportion of M2 macrophages and the levels of related cytokines IL-10， TGF-β and PDGFB， and up-regulated the levels of p-JAK1 and p-STAT6 （P<0.05）. A total of 1 214 compounds were identified from Qijia Rougan prescription， medicated serum and blank serum， and 29 ingredients were finalized by Venn analysis， including 15 blood-entry prototypes and 14 drug metabolites. Molecular docking showed that enoxolone and berberine bound more strongly to JAK1， with binding free energies of -9.6 kcal·mol^-1（1 cal≈4.184 J） and -9.1 kcal·mol^-1， respectively. Molecular dynamics simulations showed that JAK1-enoxolone and JAK1-berberine exhibited stable simulation trajectories within 100 ns， with essentially identical conformations and high protein overlap before and after simulation. Their binding free energies were -25.18 5.0.81 kcal·mol^-1 and -27.39 7.0.85 kcal·mol^-1， respectively. The number of hydrogen bonds formed between JAK1 and enoxolone ranges from 0 to 5， and most of the time can be maintained at 2-3. In vitro intervention with enoxolone or berberine significantly reduced p-JAK1 and p-STAT6 levels （P<0.05）. ConclusionQijia Rougan prescription inhibits M2 macrophage polarization in hepatic fibrosis. Enoxolone and berberine are the key effector ingredients of Qijia Rougan prescription to inhibit macrophage M2 polarization through targeting JAK1 and modulating the JAK1/STAT6 signaling pathway， thereby ameliorating hepatic fibrosis. This study provides a basis for prescription optimization， clinical application and new drug development， as well as a reference for monolithic anti-hepatic fibrosis research.

ObjectiveTo observe the clinical efficacy of Gandou Fumu Granules （GDFMG） combined with sodium dimercaptosulphonate （DMPS） on liver fibrosis in Wilson disease （WD） patients with the syndrome of phlegm and blood stasis， evaluate its effect on cuproptosis-related indicators， and explore the possible mechanisms of cuproptosis in WD-related liver fibrosis. MethodsSixty WD patients diagnosed with the syndrome of phlegm and blood stasis between January 2023 and December 2023 were randomly divided into a control group and an observation group， with 30 patients in each group. The control group received the copper chelator DMPS for the first 6 days， followed by calcium gluconate injection for the next 2 days， completing an 8-day treatment cycle. The observation group received GDFMG in addition to the treatment regimen of the control group， with both groups treated for 21 cycles. A Beckman fully automated biochemical analyzer was used to detect levels of type Ⅳ collagen （CⅣ）， hyaluronic acid （HA）， laminin （LN）， N-terminal propeptide of type Ⅲ procollagen （PⅢ-NP）， and serum copper （SCu） before and after treatment in both groups. Enzyme-linked immunosorbent assay （ELISA） was used to measure levels of ferredoxin 1 （FDX1）， lipoic acid synthetase （LIAS）， and dihydrolipoamide S-acetyltransferase （DLAT）. Atomic absorption spectroscopy measured 24-hour urine copper levels before treatment and after the 7， 14， and 21 treatment cycles in both groups. An Fibro Touch （FT） non-invasive liver fibrosis diagnostic device was used to measure liver stiffness （LSM） in both groups before and after treatment. Traditional Chinese medicine syndrome score （TCMSS） was evaluated at the same intervals. Clinical efficacy， adverse events， and safety indicators were also compared. ResultsAfter treatment， levels of CⅣ， HA， LN， and PⅢNP significantly decreased in both groups compared to pre-treatment levels （P<0.01）. The observation group showed a more pronounced reduction compared to the control group （P<0.05）. There were no statistically significant differences in SCu levels in both groups before and after treatment. After treatment， levels of FDX1，LIAS and DLAT significantly increased in both groups（P<0.01）. The observation group showed more notable improvements in these indicators than the control group （P<0.05）. After the 7， 14， 21 treatment cycles， 24-hour urine copper levels significantly increased in both groups compared to pre-treatment levels （P<0.01）. The observation group had a greater increase in 24-hour urine copper levels than the control group after treatment （P<0.05，P<0.01）， and although 24-hour urine copper levels increased after 7 cycles， a gradual decline was observed in subsequent cycles. After treatment， LSM levels significantly decreased in both groups compared to pre-treatment levels （P<0.01）， with the observation group showing a greater reduction than the control group （P<0.05）. Clinical efficacy was significantly better in the observation group than the control group （P<0.05）. No significant differences in the incidence of adverse events or safety indicators were observed between the two groups after treatment. ConclusionGDFMG combined with DMPS can reduce LSM in WD patients with liver fibrosis and the syndrome of phlegm and blood stasis， inhibit cuproptosis， and improve clinical efficacy.

Objective Through in vitro experiments,biomechanical data of the transtibial pullout suture(TPS),tendon reconstruction(TR),and tendon reconstruction with suture augmentation(TRS)were collected,so as to evaluate the biomechanical effectiveness of tendon reconstruction for repairing medial meniscus posterior root tear(MMPRT).Methods Eighteen porcine knee joint models were divided into TPS,TR,and TRS groups.Sutures were used to fix the meniscal root in TPS group.Tendons were passed through an incision at the meniscal root in TR group.Tendons were passed through an incision at the meniscal root and secured at tendon-meniscus contact area with additional sutures in TRS group.The sutures and tendons were pulled out through tibial tunnels and fixed at the anteromedial tibia.All groups underwent failure load tests,and ultimate failure load,displacement at failure load,load at clinical failure,stiffness,and failure modes of the samples were recorded.Results The maximum failure load in TPS group was significantly higher than that in TR group(P＜0.05),but there was no significant difference between TPS group and TRS group(P＞0.05).The maximum failure load in TRS group was significantly higher than that in TR group(P＜0.05).The displacement under failure load in TR group and TRS group was significantly lower than that in TPS group(P＜0.05),but there was no significant difference between TR group and TRS group(P＞0.05).There were no significant differences in the load under clinical failure among the 3 groups(P＞0.05).The stiffness of TRS group was significantly greater than that of TPS group(P＜0.05),but no significant difference was observed between TR group and TPS group,as well as between TR group and TRS group(P＞0.05).All failures were caused by suture or tendon cutting through the meniscus.Conclusions The tendon reconstruction techniques is superior to the TPS in terms of failure displacement and stiffness,while the TRS further enhances the stability of the repair.

Objectives:To investigate the predictive value of Murray's law-based quantitative flow ratio(μQFR)in side branches for long-term clinical prognosis in patients with non-left main bifurcation lesions who underwent simple main branch stenting,and to provide a potential functional assessment standard for intervention decision-making on coronary bifurcation lesions.Methods:A retrospective analysis was conducted in 408 patients with non-left main bifurcation lesions who underwent simple main branch stenting at Lianyungang First People's Hospital and Nanjing First Hospital between July 2018 and January 2021.The study utilized third-generation QFR software to analyze pre-and post-procedure anatomical and functional parameters of the target lesion's main branch and key branches.The primary endpoint was target vessel failure(TVF)events during the 3-year follow-up.Patients were stratified into TVF and non-TVF groups.Baseline characteristics,procedural data,and pre-/post-procedural parameters of target vessels were compared between groups.Multivariable Cox regression was performed to identify predictors of TVF.Diagnostic efficacy of predictors was evaluated using area under the receiver operating characteristic(ROC)curve(AUC)with DeLong's method for comparison.Patients were dichotomized based on the optimal cutoffof post-procedural side branch μQFR,with TVF incidence rates compared via Cox regression and Kaplan-Meier analysis.Results:During 3-year follow-up,54 patients(13.2%)experienced TVF(TVF group),data were compared with 354 patients(86.76%)without TVF(non-TVF group).The TVF group showed higher post-procedural side branch diameter stenosis([32.93±17.80]%vs.[22.62±11.96]%,P<0.001)and lower μQFR(0.80±0.10 vs.0.89±0.07,P<0.001).Multivariate Cox regression identified higher post-procedural side branch μQFR as an independent protective factor against 3-year TVF(per 0.01 increase:HR=0.903,95%CI:0.850-0.959,P<0.001).ROC curves indicated that post-procedural side branch μQFR had moderate diagnostic efficacy for predicting 3-year TVF(AUC=0.769,95%CI:0.678-0.861,P<0.001),with a significantly higher AUC value than post-operative side branch area stenosis and minimal lumen diameter(both P<0.001),the optimal cutoffvalue was 0.84.Multivariate Cox regression and Kaplan-Meier survival analysis revealed markedly higher 3-year TVF rates in patients with μQFR≤0.84 compared to patients with μQFR>0.84(HR=4.007,95%CI:2.342-6.855,P<0.001;28.3%vs.7.9%,log-rank P<0.001).Conclusions:For patients with bifurcation lesions not involving the left main,the immediate post-procedural side branch μQFR could better predict 3-year TVF than anatomical indices.Maintaining post-stenting side branch μQFR>0.84 may optimize clinical outcomes when using a single-stent strategy.

Objective:To analyze the clinical features of patients with traumatic optic neuropathy (TON) and to explore its clinical patterns and treatment outcomes.Methods:A retrospective analysis was conducted on data from 323 patients (334 eyes) with TON, who were treated in the Department of Otorhinolaryngology Head and Neck Surgery, the Affiliated Hospital of Qingdao University from April 1999 to October 2024. Among these patients, 288 were male and 35 were female, with ages ranging from 4 to 70 years. All patients were followed up for a period of 6 to 24 months, with the final follow-up visual acuity recorded as the ultimate visual outcome. The visual acuity evaluation criteria were classified into five levels: no light perception, light perception, hand movement in front of the eye, counting fingers at 1 meter, and "chart-visible acuity". A treatment outcome was deemed effective if the post-treatment visual acuity improved by one level or more compared to pre-treatment, or if the chart-visible acuity improved by two lines or more on the logMAR chart. The clinical characteristics of patients, causes of injury, complications, treatment methods, and changes in visual acuity before and after treatment were summarized. Logistic regression analyses were performed to identify the influencing factors affecting treatment efficacy.Results:TON occurred mostly in young (215/323, 66.56%) males (288/323, 89.16%), the majority of patients came from villages and towns (236/323, 73.07%). Traffic accidents (232/323, 71.83%) remained the main etiology. Most patients had craniofacial injuries and other bodily injuries. The effective rate of vision improvement was 50.30% (168/334). Multiple logistic regression analyses identified that residual vision (light perception or better) at presentation ( OR=3.26, P<0.001) and receiving treatment within 7 days after injury ( OR=2.04, P=0.008) were protective factors on visual acuity recovery, while the presence of orbital wall fracture was a risk factor for visual acuity recovery ( OR=0.26, P<0.001). Additionally, undergoing surgical treatment was a protective factor for visual improvement in patients with no light perception ( OR=2.94, P=0.007). For patients with residual vision at presentation, orbital wall fracture was a significant risk factor ( OR=0.28, P=0.009). Conclusions:TON is more prevalent in young males and is primarily caused by traffic accidents, leading to a poor prognosis. Timely medical intervention following injury significantly influences prognostic outcomes. Early surgical intervention (within 7 days) is recommended, particularly for patients with no light perception at presentation.

Objective:To analyze the clinical features of patients with traumatic optic neuropathy (TON) and to explore its clinical patterns and treatment outcomes.Methods:A retrospective analysis was conducted on data from 323 patients (334 eyes) with TON, who were treated in the Department of Otorhinolaryngology Head and Neck Surgery, the Affiliated Hospital of Qingdao University from April 1999 to October 2024. Among these patients, 288 were male and 35 were female, with ages ranging from 4 to 70 years. All patients were followed up for a period of 6 to 24 months, with the final follow-up visual acuity recorded as the ultimate visual outcome. The visual acuity evaluation criteria were classified into five levels: no light perception, light perception, hand movement in front of the eye, counting fingers at 1 meter, and "chart-visible acuity". A treatment outcome was deemed effective if the post-treatment visual acuity improved by one level or more compared to pre-treatment, or if the chart-visible acuity improved by two lines or more on the logMAR chart. The clinical characteristics of patients, causes of injury, complications, treatment methods, and changes in visual acuity before and after treatment were summarized. Logistic regression analyses were performed to identify the influencing factors affecting treatment efficacy.Results:TON occurred mostly in young (215/323, 66.56%) males (288/323, 89.16%), the majority of patients came from villages and towns (236/323, 73.07%). Traffic accidents (232/323, 71.83%) remained the main etiology. Most patients had craniofacial injuries and other bodily injuries. The effective rate of vision improvement was 50.30% (168/334). Multiple logistic regression analyses identified that residual vision (light perception or better) at presentation ( OR=3.26, P<0.001) and receiving treatment within 7 days after injury ( OR=2.04, P=0.008) were protective factors on visual acuity recovery, while the presence of orbital wall fracture was a risk factor for visual acuity recovery ( OR=0.26, P<0.001). Additionally, undergoing surgical treatment was a protective factor for visual improvement in patients with no light perception ( OR=2.94, P=0.007). For patients with residual vision at presentation, orbital wall fracture was a significant risk factor ( OR=0.28, P=0.009). Conclusions:TON is more prevalent in young males and is primarily caused by traffic accidents, leading to a poor prognosis. Timely medical intervention following injury significantly influences prognostic outcomes. Early surgical intervention (within 7 days) is recommended, particularly for patients with no light perception at presentation.

AIM To optimize the extraction process for Bletillae Rhizoma,and to evaluate its anti-oxidant,tyrosinase inhibitory activities.METHODS With ultrasound time,ethanol concentration and solid-liquid ratio as influencing factors,the total extraction content of gastrodin,protocatechualdehyde,p-hydroxybenzaldehyde,1,4-bis[4-(gluconoxy)benzyl]-2-isobutylmalate-2-glucoside,1,4-bis[4-(gluconoxy)benzyl]-2-isobutylmalate,yam Ⅲ,dihydropinosin and 3'-O-methylyam Ⅲ as an evaluation index,the extraction process was optimized by Box-Behnken response surface method.Subsequently,the extract's scavenging effects on DPPH,ABTS+free radicals,and inhibitory ability on tyrosinase were determined.RESULTS The optimal conditions were determined to be 49 min for ultrasound time,55％for ethanol concentration,1∶30 for solid-liquid ratio,and 2 times for extraction frequency,the total extraction content was 13.18 mg/g.The extract demonstrated the IC50 of 10.12,314.07 and 1.70 μg/g on DPPH,ABTS+free radicals and tyrosinase,respectively.CONCLUSION This simple,reliable and stable method can be used for the extraction for Bletillae Rhizoma with strong anti-oxidant,tyrosinase inhibitory activities.