ObjectiveTo systematically evaluate the content differences of 4 components in Leonuri Herba granules， reveal the quality fluctuation patterns of products from the same and different manufacturers， providing scientific basis for the optimization of production process and quality control. MethodsHigh performance liquid chromatography-diode array detector-charged aerosol detector（HPLC-DAD-CAD） was employed to determine the contents of 4 components（syringic acid， leonurine hydrochloride， ferulic acid， and stachydrine hydrochloride） in samples from 19 manufacturers（53 batches， 159 boxes）. Additionally， fingerprint profiles were constructed， and the fingerprint dissimilarity（P_S） and relative standard deviation（RSD） of different samples from the same manufacturer were calculated. A principal component analysis（PCA） model was established with P_S and the RSD values of the 4 components as variables to classify the manufacturers. Finally， samples from 5 manufacturers（M1-M5） covering three consistency groups were selected to calculate three quality consistency parameters， namely intra-batch consistency（P_A）， inter-batch consistency（P_B）， and P_S. Then， PCA was performed with P_A， P_B， and P_S of these 5 manufacturers as variables. ResultsThe average total content of the 4 index components per bag across the 19 manufacturers ranged from 41.10 mg to 97.54 mg. Among them， the content of stachydrine hydrochloride（a pharmacopoeial quality control component） was 32.46-72.70 mg per bag， all meeting the requirements of the 2025 edition of the Pharmacopoeia of the People's Republic of China， with RSD of 1.7%-17.1%. The content ranges of the other 3 components were as follows：syringic acid of 1.43-41.92 mg per bag， leonurine hydrochloride of 0.67-11.85 mg per bag， and ferulic acid of 0.11-3.81 mg per bag. Notably， leonurine hydrochloride exhibited the most significant content fluctuation among samples from the same manufacturer（RSD of 4.8%-59.2%）. PCA results showed that the 19 manufacturers could be classified into 3 categories. Samples from 8 manufacturers（M2， M6， M7， M8， M10， M15， M17， M18） demonstrated relatively high consistency， five manufacturers（M3， M9， M12， M13， M14） showed moderate consistency， six manufacturers（M1， M4， M5， M11， M16， M19） exhibited low consistency. The two methods yielded consistent classification results for the 5 representative manufacturers， verifying the reliability of the proposed method. Among these， manufacturer M2 showed the best quality consistency and the highest total content of indicator components among M1-M5. ConclusionThe HPLC-DAD-CAD multi-detector hyphenation technology established in this study enables the accurate detection of 4 components in Leonuri Herba granules. Significant differences in the total content of these four components are observed among products from 19 manufacturers. The application of 2 consistency evaluation methods combined with PCA can effectively classify their consistency into 3 categories， and the classification results of the 2 methods are highly consistent. This study provides scientific basis for the process optimization and quality standard improvement of Leonuri Herba granules.

ObjectiveTo systematically evaluate the content differences of 4 components in Leonuri Herba granules， reveal the quality fluctuation patterns of products from the same and different manufacturers， providing scientific basis for the optimization of production process and quality control. MethodsHigh performance liquid chromatography-diode array detector-charged aerosol detector（HPLC-DAD-CAD） was employed to determine the contents of 4 components（syringic acid， leonurine hydrochloride， ferulic acid， and stachydrine hydrochloride） in samples from 19 manufacturers（53 batches， 159 boxes）. Additionally， fingerprint profiles were constructed， and the fingerprint dissimilarity（P_S） and relative standard deviation（RSD） of different samples from the same manufacturer were calculated. A principal component analysis（PCA） model was established with P_S and the RSD values of the 4 components as variables to classify the manufacturers. Finally， samples from 5 manufacturers（M1-M5） covering three consistency groups were selected to calculate three quality consistency parameters， namely intra-batch consistency（P_A）， inter-batch consistency（P_B）， and P_S. Then， PCA was performed with P_A， P_B， and P_S of these 5 manufacturers as variables. ResultsThe average total content of the 4 index components per bag across the 19 manufacturers ranged from 41.10 mg to 97.54 mg. Among them， the content of stachydrine hydrochloride（a pharmacopoeial quality control component） was 32.46-72.70 mg per bag， all meeting the requirements of the 2025 edition of the Pharmacopoeia of the People's Republic of China， with RSD of 1.7%-17.1%. The content ranges of the other 3 components were as follows：syringic acid of 1.43-41.92 mg per bag， leonurine hydrochloride of 0.67-11.85 mg per bag， and ferulic acid of 0.11-3.81 mg per bag. Notably， leonurine hydrochloride exhibited the most significant content fluctuation among samples from the same manufacturer（RSD of 4.8%-59.2%）. PCA results showed that the 19 manufacturers could be classified into 3 categories. Samples from 8 manufacturers（M2， M6， M7， M8， M10， M15， M17， M18） demonstrated relatively high consistency， five manufacturers（M3， M9， M12， M13， M14） showed moderate consistency， six manufacturers（M1， M4， M5， M11， M16， M19） exhibited low consistency. The two methods yielded consistent classification results for the 5 representative manufacturers， verifying the reliability of the proposed method. Among these， manufacturer M2 showed the best quality consistency and the highest total content of indicator components among M1-M5. ConclusionThe HPLC-DAD-CAD multi-detector hyphenation technology established in this study enables the accurate detection of 4 components in Leonuri Herba granules. Significant differences in the total content of these four components are observed among products from 19 manufacturers. The application of 2 consistency evaluation methods combined with PCA can effectively classify their consistency into 3 categories， and the classification results of the 2 methods are highly consistent. This study provides scientific basis for the process optimization and quality standard improvement of Leonuri Herba granules.

Panvascular disease， with vascular diseases as the common pathological feature， is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart， brain， kidney， and limbs. It is one of the leading causes of death for Chinese residents at present. Previously， due to the narrow branches of disciplines， too much attention was paid to local lesions， resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies， makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel''， ''meridians''， ''visceral manifestation''， and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover， those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm， stasis， stagnation， and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm''， and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis， cerebral atherosclerosis， and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM， and the TCM treatment mainly invigorates Qi and promotes blood circulation， which can inhibit venous thrombosis， improve venous ulcers， and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM， and the treatment mainly promotes Qi and dredges collaterals， which has a good effect on coronary microvascular lesions， diabetic microvascular lesions， pulmonary microvascular lesions， and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion， which can promote lymphangiogenesis and enhance lymphatic reflux. In addition， the combination of TCM and modern technology， especially the application of artificial intelligence， can improve the efficiency of early identification and personalized treatment， resulting in early screening and comprehensive management of panvascular diseases. Therefore， TCM will play a vital role in the prevention and treatment of panvascular diseases.

Panvascular disease， with vascular diseases as the common pathological feature， is mainly manifested as atherosclerosis. Panvascular disease mainly affects the important organs of the heart， brain， kidney， and limbs. It is one of the leading causes of death for Chinese residents at present. Previously， due to the narrow branches of disciplines， too much attention was paid to local lesions， resulting in the neglect of panvascular disease as a systemic one. The fact that panvascular disease has overall pathology and comprehensive and individualized treatment strategies， makes the disease highly compatible with the principles of holism concept and syndrome differentiation and treatment in traditional Chinese medicine （TCM）. It is believed that blood stasis is the core pathogenesis of atherosclerosis and is involved in the whole process of atherosclerosis. The theories of ''blood vessel''， ''meridians''， ''visceral manifestation''， and ''organs-meridians'' in TCM are helpful to comprehensively understand the complexity of panvascular diseases. Moreover， those theories can provide systematic treatment strategies. The TCM syndromes of panvascular diseases evolve from ''phlegm， stasis， stagnation， and deficiency''. Panvascular arteriosclerosis is related to the syndrome of ''stasis and phlegm''， and the treatment mainly promotes blood circulation and removes phlegm. There are different specific drugs and mechanisms of action for coronary atherosclerosis， cerebral atherosclerosis， and renal artery atherosclerotic stenosis. Panvascular venous lesions are related to the syndrome of ''deficiency and stasis'' in TCM， and the TCM treatment mainly invigorates Qi and promotes blood circulation， which can inhibit venous thrombosis， improve venous ulcers， and resist venous endothelial damage. Panvascular microcirculatory lesions are inseparable from the ''stagnation and stasis'' in TCM， and the treatment mainly promotes Qi and dredges collaterals， which has a good effect on coronary microvascular lesions， diabetic microvascular lesions， pulmonary microvascular lesions， and pancreatic microvascular lesions. Panvascular lymphatic lesions are related to the syndrome of ''water and stasis'' in TCM. The treatment method focuses on promoting blood circulation and water excretion， which can promote lymphangiogenesis and enhance lymphatic reflux. In addition， the combination of TCM and modern technology， especially the application of artificial intelligence， can improve the efficiency of early identification and personalized treatment， resulting in early screening and comprehensive management of panvascular diseases. Therefore， TCM will play a vital role in the prevention and treatment of panvascular diseases.

ObjectiveTo establish the fingerprints of 15 batches of Hengzhi Kechuan capsules， to quantitatively analyze 10 index components， and to evaluate the quality uniformity of samples from different batches. MethodsThe fingerprints and quantitative analysis of Hengzhi Kechuan capsules were established by a combination method of high performance liquid chromatography coupled with diode array detector and charged aerosol detector（HPLC-DAD-CAD）， adenosine， guanosine， vanillic acid， safflomin A， agarotetrol， naringin， hesperidin， militarine， ginsenoside Rb₁， and glycyrrhizic acid were selected as quality attribute indexes. A total of 15 batches of Hengzhi Kechuan capsules from 2022 to 2024（3 boxes per batch） were qualitatively and quantitatively analyzed， and the quality uniformity level of the manufacturers was characterized by parameters of intra-batch consistency（P_A） and inter-batch consistency（P_B）. The homogeneity and difference of quality attribute indexes of samples from different years were analyzed by heatmap clustering analysis. ResultsHPLC fingerprints and quantitative method of Hengzhi Kechuan capsules were established， and the methods could be used for qualitative and quantitative analysis of this preparation， which was found to be stable and reliable by method validation. The similarity of fingerprints of 15 batches of samples was 0.887-0.975， a total of 13 common peaks were calibrated， and 10 common peaks were designated， all of which were quality attribute index components. The results of quantitative analysis showed that the contents of the above 10 ingredients in the samples were 0.038-0.078， 0.115-0.251， 0.007-0.018， 0.291-0.673， 0.122-0.257， 0.887-1.905， 1.841-3.364， 1.412-2.450， 2.207-3.112， 0.650-1.161， respectively. And the contents of ginsenoside Rb₁ and glycyrrhizic acid met the limit requirements in the 2020 edition of Chinese Pharmacopoeia. For the samples from 15 batches， the P_A values of the 10 index components were all <10%， indicating good intra-batch homogeneity， and the P_B values ranged from 33.86% to 92.97%， suggesting that the inter-batch homogeneity was poor. Heatmap clustering analysis showed that the samples from different years were clustered into separate categories， and adenosine， guanosine， safflomin A， naringin， hesperidin and agarotetrol were the main differential components. ConclusionThe intra-annual quality uniformity of Hengzhi Kechuan capsules is good and the inter-annual quality uniformity is insufficient， which may be related to the quality difference of Pinellinae Rhizoma Praeparatum， Carthami Flos， Citri Sarcodactylis Fructus， Citri Reticulatae Pericarpium， Aquilariae Lignum Resinatum， Citri Fructus， etc. In this study， the fingerprint and multi-indicator determination method of Hengzhi Kechuan capsules was established， which can be used for more accurate and efficient quality control and standardization enhancement.

OBJECTIVE: To reveal the effects and potential mechanisms by which synaptic vesicle glycoprotein 2A (SV2A) influences the distribution of amyloid precursor protein (APP) in the trans-Golgi network (TGN), endolysosomal system, and cell membranes and to reveal the effects of SV2A on APP amyloid degradation. METHODS: Colocalization analysis of APP with specific tagged proteins in the TGN, ensolysosomal system, and cell membrane was performed to explore the effects of SV2A on the intracellular transport of APP. APP, β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expressions, and APP cleavage products levels were investigated to observe the effects of SV2A on APP amyloidogenic processing. RESULTS: APP localization was reduced in the TGN, early endosomes, late endosomes, and lysosomes, whereas it was increased in the recycling endosomes and cell membrane of SV2A-overexpressed neurons. Moreover, Arl5b (ADP-ribosylation factor 5b), a protein responsible for transporting APP from the TGN to early endosomes, was upregulated by SV2A. SV2A overexpression also decreased APP transport from the cell membrane to early endosomes by downregulating APP endocytosis. In addition, products of APP amyloid degradation, including sAPPβ, Aβ _1-42, and Aβ _1-40, were decreased in SV2A-overexpressed cells. CONCLUSION These results demonstrated that SV2A promotes APP transport from the TGN to early endosomes by upregulating Arl5b and promoting APP transport from early endosomes to recycling endosomes-cell membrane pathway, which slows APP amyloid degradation.
Amyloid beta-Protein Precursor/genetics* ; Membrane Glycoproteins/genetics* ; Animals ; Protein Transport ; Nerve Tissue Proteins/genetics* ; Humans ; Mice ; Endosomes/metabolism* ; trans-Golgi Network/metabolism*

The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose-catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16 ℃ in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni-NTA affinity column.Size-exclusion chromatography and SDS-PAGE analysis demonstrated that the puri-fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD+as a coenzyme to NADP+.The optimal temperature and pH of the TeXDH were 40 ℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26％of the initial enzyme activity,while the divalent metal ions Mg2+or Ca2+could recover the enzyme activity of TeXDH,reaching 103.32％and 110.69％of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn2+,Ni2+,Cu2+,Zn2+,Co2+,and Cd2+significantly inhibited the activity of TeXDH.ICP-MS and molecular doc-king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn2+ions and 1 mol/L Mg2+ion.Further-more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.

Objective:To evaluate the clinical utility of an intelligent endoscope transportation system in the digestive endoscopy center.Methods:A parallel-group controlled trial was conducted at Digestive Endoscopy Center of Qilu Hospital of Shandong University from June 1st to December 31st 2024, comparing robotic intelligent endoscope transport (experimental group) versus manual transport (control group). Performance metrics, including response time, transportation speed, labor efficiency, contamination prevention, closed-loop traceability, and nursing staff satisfaction, were statistically analyzed. Full-time equivalent (FTE) was introduced to quantify the operational efficiency of the experimental group.Results:The study included a total of 60 206 instances of intelligent endoscope transportation and 60 485 instances of manual transportation data. The robotic group demonstrated significantly shorter response times versus manual group for initial dispatch (51.08±14.97 seconds VS 54.44±13.61 seconds, t=35.8, P<0.001) and recovery response time (32.52±11.26 seconds VS 40.20±11.40 seconds, t=103.93, P<0.001). During the 148 days operational period, the success rate was 99.83% (60 104/60 206) and the failure rate was 0.17% (102/60 206) for robotic transports. Primary failure causes were wireless disconnection, pathfinding errors, and mechanical faults, averaging 1.05 malfunctions/month with no adverse events. The success and failure rate was 99.26% (60 043/60 485) and 0.74% (442/60 485) respectively for manual transports. Staff satisfaction was significantly higher for robotic transport in endoscopic transportation (4.65±0.55 scores VS 3.97±0.98 scores, t=96.5, P<0.001) and delivery process (4.71±0.59 scores VS 3.90±1.04 scores, t=210.3, P<0.001). and workload intensity was significantly lower (4.06±0.77 scores VS 4.48±0.63 scores, t=59.9, P=0.025). The system reduced labor requirements by 3.68 FTE, yielding annual savings of ￥657 000. Conclusion:The robotic intelligent endoscope transport system improves work efficiency, reduces nursing labor costs and physical workload, enhances job experience and satisfaction, and enables full-process smart traceability, providing a validated solution for endoscopy center logistics.

Objective To evaluate the effects of fasting and high-fat diet on the pharmacokinetics of rabeprazole sodium enteric-coated tablets in healthy Chinese subjects.Methods A single-center,randomized,open,two-agent,two-sequence,four-cycle,fully repeated crossover,single-dose trial design was used in this study,healthy subjects were assigned to receive single dose of rabeprazole sodium enteric-coated tablets 0.1 g in either fasting or high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of rabeprazole sodium enteric-coated in plasma were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS),the model method of the non-compartmental was used to calculate the pharmacokinetic parameters by Phoenix WinNonlin 8.2.Results The main pharmacokinetic parameters of rabeprazole sodium enteric-coated tablets in fasting state and high-fat diet state were as follows:Cmax were(339.63±156.47)and(318.86±132.13)ng·mL-1;t1/2 were(2.34±0.68)and(3.60±2.40)h;AUC0_t were(556.62±251.65)and(528.50±201.78)ng·mL-1·h;AUC0-∞ were(563.39±255.69)and(535.15±203.24)ng·mL-1·h;tmax were 3.65 and 6.99 h.After high-fat diet,the Cmax and AUC of rapeprazole sodium after high-fat and high-calorie diet decreased,Cmax decreased by 6.12％,AUC0-t decreased by 5.05％,AUC0-∞ decreased by 5.01％,andtmaxwas delayed by about 3.34 h.Cmax,AUC0-t and AUC0-∞ 90％confidence interval were 73.13％-115.10％,83.22％-112.28％and 83.40％-112.13％,respectively.Neither was between 85.00％-125.00％.Conclusion High-fat diet affects the absorption rate and degree of rabeprazole sodium enteric-coated,so it is suitable to be administered on an empty stomach.

Paraganglioma（PGL）is an extra-adrenal catecholamine-secreting endocrine tumor. We reported a young female patient who was admitted to the hospital with right flank pain and diagnosed with right retroperitoneal PGL with Mayo Ⅳ inferior vena cava tumor thrombus（double tumor thrombus）. After multidisciplinary consultation，right retroperitoneal PGL resection，right nephrectomy，inferior vena cava Mayo Ⅳ tumor thrombus resection and reconstruction were performed. Postoperative pathology showed that the primary tumor and inferior vena cava tumor thrombus was consistent with PGL. Genetic testing revealed a heterozygous germline nonsense mutation at c.69_70delinsTT（p.Q24*）locus of the SDHB gene in the patient. His mother was a carrier of the gene，but his father and sister did not carry the mutation. The patient recovered smoothly after surgery.