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.

ObjectiveTo systematically compare the effects of diverse electromagnetic stimulation protocols on hand function and activities of daily living (ADL) in stroke patients using network meta-analysis (NMA), and screen the optimal stimulation strategy for post-stroke hand dysfunction rehabilitation. MethodsNMA was performed in accordance with the PRISMA-NMA statement. Databases of CNKI, Wanfang data, VIP, CBM, PubMed, Web of Science and Embase were searched from database inception to April, 2026 for eligible randomized controlled trials (RCTs) comparing different electromagnetic stimulation protocols for post-stroke hand impairment. The Cochrane Risk of Bias tool and PEDro scale were used to assess methodological quality of included studies, while the GRADE system was adopted to grade evidence quality of primary outcomes of Fugl-Meyer Assessment-Upper Extremities (FMA-UE) and modified Barthel Index (MBI). After literature screening, data extraction and bias evaluation, RevMan 5.4 and Stata 17.0 were used for meta-analysis and NMA. ResultsA total of 22 RCT involving 17 electromagnetic stimulation protocols were finally included. The PEDro scores ranged from six to ten. The top five protocols for improving FMA-UE score were repetitive peripheral magnetic stimulation (rPMS) + repetitive transcranial magnetic stimulation (rTMS), intermittent theta-burst stimulation (iTBS) + rPMS, iTBS + transcranial direct current stimulation (tDCS), transcutaneous electrical acupoint stimulation (TEAS) and contralaterally controlled functional electrical stimulation (CCFES). tDCS was the most effective on MBI, followed by TEAS and iTBS+rPMS. Evidence quality for FMA-UE and MBI was moderate. Funnel plots suggested low risk of publication bias, and consistency tests verified good coherence between direct and indirect comparisons in network models. ConclusionElectromagnetic stimulation significantly facilitates upper limb and hand functional recovery, and improves ADL in stroke patients. The combined central-peripheral magnetic stimulation protocol may be the most effective on motor rehabilitation, whereas tDCS on ADL.

Chinese patent medicines are the core preparations for disease prevention and treatment in clinical traditional Chinese medicine （TCM）. Their quality is the key to ensuring safe and effective medication and promoting the high-quality development of the TCM industry. At present， the quality evaluation of Chinese patent medicines faces prominent problems， such as inadequate control of quality consistency， over-reliance on single indicators， one-sided evaluation dimensions， unstable statistical methods， and poor implementability of research findings. These defects lead to insufficient scientificity of evaluation results， making it difficult to support the implementation of policies including centralized procurement， high quality， and favorable prices for Chinese patent medicines. According to the core requirements of quality evaluation for Chinese patent medicines， this study established a four-dimensional comprehensive evaluation system encompassing consistency index（CI）， content index（MI）， effect index（EI）， and preparation index（PI）. All evaluation indicators were normalized to achieve horizontal comparability. Meanwhile， an improved radar chart was introduced to realize the visualization of evaluation results. This method can systematically integrate four types of core quality attributes： Quality consistency， component content， biological activity， and preparation characteristics. It can effectively distinguish quality differences among products of the same specification from different manufacturers. The evaluation results are unique， stable， and not affected by the addition or reduction of samples， which takes scientificity， objectivity， and operability into account. This method can provide scientific and technical support for screening high-quality Chinese patent medicines and implementing policies of centralized procurement， high quality， and favorable prices. Moreover， it has important practical significance for improving the quality evaluation system of Chinese patent medicines and advancing the standard and modern development of TCM.

ObjectiveTo establish a comprehensive evaluation framework combining multi-component quantification with daily intake in response to the challenges posed by multiple coexisting dosage forms， single-faceted quality evaluation， and ambiguous clinical equivalence of Huoxiang Zhengqi preparations， and to compare the quality differences and superiority among eight commercially available dosage forms. MethodsA total of 75 batches of Huoxiang Zhengqi preparations from 25 manufacturers were investigated. Ultra-performance liquid chromatography-triple quadrupole-tandem mass spectrometry （UPLC-QqQ-MS/MS） coupled with gas chromatography-triple quadrupole-tandem mass spectrometry （GC-QqQ-MS/MS） was adopted to simultaneously quantify 20 core marker components. Normalization was performed based on equivalent raw herb concentrations to eliminate interferences from dosage forms， excipients， and specifications. Considering the specified clinical dosage， the actual daily intake level was calculated to comprehensively evaluate component retention， content uniformity， and potential differences in in vivo exposure among different dosage forms. ResultsThe quality of Huoxiang Zhengqi preparations differed greatly among dosage forms and manufacturers. On the basis of the recommended daily doses in the package inserts， the total daily intake of the 20 tested components ranged from 3.14 to 614.30 mg·d^-1， while that of hesperidin， a quality-control marker， ranged from 0.03 to 40.65 mg·d^-1. Atractylodin was detected only in tinctures and soft capsules， with concentrations ranging from （2.68±0.01） to （5.73±0.37） mg·L^-1. The soft capsules from manufacturer M22 had the highest atractylodin level， while atractylodin was not detected in the other dosage forms. Nucleosides were most abundant in the oral liquids and tinctures （M4 to M13）. The tincture from manufacturer M5 showed the highest nucleoside level of 29.12 mg·L^-1， whereas the granules had the lowest nucleoside levels， with that of M23 being only 3.48 mg·L^-1. Perillae Folium-related components varied greatly among batches， with an relative standard deviation （RSD） of 87.55%. The daily intake of hesperidin from all three granule products was below 3.6 mg·d^-1， the reference value calculated for Huoxiang Zhengqi Shui according to the 2025 edition of the Chinese Pharmacopoeia. ConclusionThe levels of active components differed significantly among different dosage forms of Huoxiang Zhengqi preparations. Tinctures contained more types and higher overall levels of active components， while soft capsules were better at preserving volatile components. Granules and dripping pills had lower overall levels of active components. The comprehensive evaluation method established in this study can provide a basis for the quality control， process optimization， and the selection of high-quality products.

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2D^mutBTG2^mut had poorer OS than those with KMT2D^wt BTG2^mut (P=0.07) and KMT2D^wt BTG2^wt (P=0.05). On the contrary, patients with KMT2D^mut CD79B^mut had better OS than those with KMT2D^mut CD79B^wt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2D^mutBTG2^mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.

To reduce the dependency on high-carbon-load chromatographic columns,a new method has been established for the determination of the content of docusate sodium using ion-pair high-performance liquid chromatography (IP-HPLC). Tetrapropylammonium chloride was used as the ion-pair reagent with a mobile phase, composition of acetonitrile:10 mmol/L tetrapropylammonium chloride solution = 66∶34, adjusting pH to 6.5 with 0.1% phosphoric acid solution,flow rate of 1.5 mL/min, detection wavelength of 214 nm,column temperature of 35 °C, and an injection volume of 25 μL,and quantified by an external standard method. The main peak of docusate sodium exhibited a tailing factor of 1.34. The method showed good linearity within the range of 0.02 mg/mL to 0.40 mg/mL, with a correlation coefficient (r) of 0.999 9. It also demonstrated good repeatability, with recovery ranging from 97.0% to 98.2% (n=6). The quantification limit was 3.31 μg/mL, and the detection limit was 2.76 μg/mL.In summary,the new method shows good durability, a wide linear range, and high sensitivity, it is suitable for the determination of docusate sodium.

Combined vaccines can simplify the vaccination process, improve coverage rates, reduce the risk of adverse events following immunization, lower social costs, and improve the timeliness of childhood vaccination. This article focuses on multi-component vaccines based on the diphtheria-tetanus-pertussis containing vaccine. Globally, multiple combined vaccines have been developed and marketed, but the development of combined vaccine is still in its infancy stage in China, with limited vaccine types and doses available. The research, development, and application of combined vaccines still face numerous challenges in China, including technical challenges in research and development, as well as insufficient motivation for research and development. Additionally, the high cost of existing combined vaccines, coupled with low public awareness and weak vaccination intentions, significantly hinders their widespread application, China should continue to rigorously implement the Vaccine Administration Law of the People's Republic of China, promote innovative development of combined vaccines, increase public awareness, strengthen child guardians' confidence in vaccination, and improve the accessibility and affordability of combined vaccines to protect public health across all life stages.

Objective:To analyze the clinical characteristics of patients with pregnancy-related chronic pain visiting the pain clinic.Methods:The number of pregnant patients who completed a pregnancy registration at the Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical University from 2022 to 2024 was collected. The medical records were reviewed to identify the patients who visited the department of pain of our hospital due to chronic pain related to pregnancy. The clinical characteristics such as the visiting situation, gestational weeks, age and types of pain were analyzed.Results:From 2022 to 2024, the total number of registered pregnant patients was 64, 818, of which, 2, 224 cases visited the pain clinic, and the annual proportions of pregnancy-related chronic pain visits were 2.540%, 3.836% and 3.889% respectively. Among the patients who attended the clinic, 77.97% were pregnant (5.82% in early pregnancy, 41.93% in mid-pregnancy, and 52.25% in late pregnancy), and 21.03% were postpartum patients. A total of 83.72% were aged 20-34 yr. The types of pain were pelvic girdle pain (40.96%), limb joint pain (28.82%), low back pain (14.16%), cervical spondylosis (3.64%), peripheral nerve entrapment syndrome (3.42%), headache (2.97%), chest and back pain (2.79%), pelvic and perineal pain (1.66%), neuralgia (0.94%) and other pains (0.63%).Conclusions:From 2022 to 2024, the proportion of registered pregnant women at our hospital who visited to the pain clinic due to pregnancy-related chronic pain increases year by year. The common types of pain are pelvic girdle pain, limb joint pain and low back pain.