BACKGROUND:Eucommia ulmoides has a certain osteogenic effect,which can promote the proliferation and differentiation of osteoblasts.However,it is unclear whether Eucommia ulmoides has effects on alveolar bone formation and Wnt/β-Catenin signaling pathway. OBJECTIVE:To investigate the mechanism by which Eucommia ulmoides promotes alveolar bone formation in ovariectomized rats based on the Wnt/β-Catenin signaling pathway. METHODS:Sixty female Sprague-Dawley rats were selected and randomly divided into five groups:blank control group,sham-operation group,model group,low-dose group Eucommia ulmoides group,and high-dose Eucommia ulmoides group,with twelve rats in each group.Osteoporosis animal models were constructed by bilateral oophorectomy in the model group and the low-dose and high-dose Eucommia ulmoides groups.The sham-operation group underwent the same method to remove adipose tissue of equal mass around the bilateral ovaries.Three months after surgery,the low-and high-dose Eucommia ulmoides groups were given 2.1 g/kg/d and 4.2 g/kg/d Eucommia ulmoides by gavage,respectively.The sham-operation group and model group were given the same amount of physiological saline by gavage.After 12 weeks of drug intervention,the changes in alveolar bone mass of rats in each group were observed through Micro-CT;hematoxylin-eosin staining was used to observe the pathological structural changes of alveolar bone in rats;enzyme linked immunosorbent assay was used to detect the expression levels of alkaline phosphatase and osteocalcin in the serum of rats;western blot was used to detect the expression levels of β-Catenin and Frizzled9 receptor proteins in the alveolar bone of rats;and real-time fluorescence quantitative PCR was used to detect the expression of osteocalcin,Runt-related transcription factor 2(Runx2),alkaline phosphatase,β-catenin,and frizzled9 mRNAs in alveolar bone tissues of rats. RESULTS AND CONCLUSION:Compared with the blank control group,bone volume fraction,trabecular number,trabecular thickness,and bone mineral density were reduced in the model group(P＜0.05),and trabecular separation was elevated(P＜0.05).Pathological observation showed that the arrangement of trabeculae was disordered and irregular,the trabeculae were thinned or broken,and the marrow cavity was enlarged in the model group,with a significant reduction in bone volume;the level of alkaline phosphatase in the serum was increased(P＜0.05),and the level of osteocalcin was decreased(P＜0.05);mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were decreased(P＜0.05);protein expression of β-Catenin and Frizzled9 was decreased(P＜0.05).Compared with the model group,the low-and high-dose Eucommia ulmoides groups showed an increase in bone volume fraction,trabecular number,trabecular thickness,and bone mineral density(P＜0.05)and a decrease in trabecular separation(P＜0.05).In the low-and high-dose Eucommia ulmoides groups,bone trabeculae were slightly aligned and thickened,with a significant increase in bone mass.Compared with the model group,the serum level of alkaline phosphatase was reduced(P＜0.05)and the serum level of osteocalcin was elevated(P＜0.05)in the low-and high-dose Eucommia ulmoides groups.Compared with the model group,the mRNA expression of alkaline phosphatase,osteocalcin,Runx2,β-catenin,and frizzled9 were increased in the low-and high-dose Eucommia ulmoides groups(P＜0.05).Compared with the model group,the protein expression of Frizzled9 was increased in the low-dose Eucommia ulmoides group(P＜0.05),while the protein expression of β-Catenin and Frizzled9 was increased in the high-dose Eucommia ulmoides group(P＜0.05).Compared with the low-dose Eucommia ulmoides group,the high-dose Eucommia ulmoides group had a more significant improvement in the above indexes.To conclude,Eucommia ulmoides can effectively promote the alveolar bone formation,and its mechanism of action might be related to the activation of the Wnt/β-catenin signaling pathway.

ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine （TCM） medication rule of children with primary nephrotic syndrome （PNS） in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected， and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria， an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting， association rule analysis， and cluster analysis were carried out on TCM in the prescription， and the high-frequent drugs were analyzed. Results（1） General information： A total of 711 children were included， consisting of 522 males （73.42%） and 189 females （26.58%）. The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age， and the average age of onset was （4.74 ± 3.48） years old. （2） Clinical treatment plan and use of immunosuppressive agents： Of the 711 children with PNS， 237 were treated with hormone alone （32.33%）， and 474 （66.67%） received immunosuppressive agents combined with hormones. In the initial treatment， hormone combined with Tacrolimus （TAC） was the preferred treatment （32.91%）. For children with refractory PNS who exhibited poor clinical efficacy， Rituximab （RTX） was mostly used for treatment， with a ratio of up to 23.63%. （3） TCM syndrome and medication rule： In PNS syndrome differentiation， Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases， accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases， accounting for 16.60%. A total of 711 children were included， of which 706 children were treated with TCM. This involved a total of 706 prescriptions， 226 TCM， and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae （81.16%）， Radix Astragali （71.81%）， Poria （68.84%）， Rhizoma Atractylodis Macrocephalae （63.60%）， and Fructus Corni （57.37%）. The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest， and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children， TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS， RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali， Poria， Rhizoma Atractylodis Macrocephalae， and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.

ObjectiveTo analyze the clinical treatment plan and traditional Chinese medicine （TCM） medication rule of children with primary nephrotic syndrome （PNS） in the First Affiliated Hospital of Henan University of Chinese Medicine. MethodsThe gender and age of children firstly diagnosed with nephrotic syndrome in the pediatric nephrology department of the First Affiliated Hospital of Henan University of Chinese Medicine from November 2019 to December 2022 were collected， and the use of immunosuppressive agents and related frequencies were counted. According to the inclusion and exclusion criteria， an independent TCM prescription database for children with nephrotic syndrome was established. Excel was used to analyze the relevant information of the literature. The frequency counting， association rule analysis， and cluster analysis were carried out on TCM in the prescription， and the high-frequent drugs were analyzed. Results（1） General information： A total of 711 children were included， consisting of 522 males （73.42%） and 189 females （26.58%）. The ratio of male to female was about 2.76∶1. The disease mainly occurred in infants and preschool age， and the average age of onset was （4.74 ± 3.48） years old. （2） Clinical treatment plan and use of immunosuppressive agents： Of the 711 children with PNS， 237 were treated with hormone alone （32.33%）， and 474 （66.67%） received immunosuppressive agents combined with hormones. In the initial treatment， hormone combined with Tacrolimus （TAC） was the preferred treatment （32.91%）. For children with refractory PNS who exhibited poor clinical efficacy， Rituximab （RTX） was mostly used for treatment， with a ratio of up to 23.63%. （3） TCM syndrome and medication rule： In PNS syndrome differentiation， Qi and Yin deficiency was identified as the main syndrome. This involved a total of 477 cases， accounting for 67.09%. Yang deficiency of spleen and kidney was observed in 118 cases， accounting for 16.60%. A total of 711 children were included， of which 706 children were treated with TCM. This involved a total of 706 prescriptions， 226 TCM， and 9 793 frequencies. There were 30 herbs used more than 95 times. The top five TCM were Radix et Rhizoma Glycyrrhizae （81.16%）， Radix Astragali （71.81%）， Poria （68.84%）， Rhizoma Atractylodis Macrocephalae （63.60%）， and Fructus Corni （57.37%）. The drug association rules and network diagram showed that the combination of ''Radix Astragali-Rhizoma Atractylodis Macrocephalae-Poria'' was the closest， and five types of combinations were obtained by cluster analysis. ConclusionIn the diagnosis and treatment of PNS in children， TAC combined with hormones shows good clinical efficacy and high safety. For children with refractory PNS， RTX combined with hormones can be used. TCM medication for PNS should follow the basic principles of strengthening the body and vital Qi and make good use of drugs such as Radix Astragali， Poria， Rhizoma Atractylodis Macrocephalae， and cornus to regulate the Yin and Yang balance and achieve better clinical efficacy.

ObjectiveBased on ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， network pharmacology and molecular docking techniques， to explore the pharmacodynamic material basis and mechanism of Renshen Wuweizi Tang in treating spleen-lung Qi deficiency syndrome. MethodsThe chemical components in the decoction of Renshen Wuweizi Tang were systematically characterized and identified by UPLC-Q-TOF-MS/MS， and network pharmacology was used to screen potential active ingredients， collect component targets and gene sets related to spleen-lung Qi deficiency syndrome， and obtain protein interaction relationships through STRING. Cytoscape 3.9.1 was used to construct a "formula-syndrome" association network and calculate topological feature values. Gene ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analysis were performed on core genes to explore potential pharmacodynamic links， the average shortest path between the formula-drug target network and the pharmacodynamic link gene network was calculated to discover dominant pharmacodynamic links， and MCODE plugin was used to identify core gene clusters from the dominant pharmacodynamic links， which were validated using Gene Expression Omnibus（GEO）， and molecular docking was performed between key components and core targets. ResultsOne hundred and thirty-seven components were identified in the negative ion mode， and eighty components were identified in the positive ion mode. After deduplication， a total of 185 components were identified， mainly composed of triterpenoid saponins（49） and flavonoids（54）. Based on the "formula-syndrome" correlation network analysis， energy metabolism was determined to be the dominant pharmacodynamic link of Renshen Wuweizi Tang in the treatment of spleen-lung Qi deficiency syndrome. The results of molecular docking showed that 7 components（adenosine， atractylenolide Ⅱ， atractylenolide Ⅲ， ginsenoside Rg₁， glycyrrhizin B₂， glycyrrhizin E₂ and campesterol） from 4 medicinal materials（Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Glycyrrhizae Radix et Rhizoma and Poria） in this formula might regulate energy metabolism by acting on 6 targets， namely cyclic adenosine monophosphate-response element binding protein 1（CREB1）， glyceraldehyde-3-phosphate dehydrogenase（GAPDH）， interleukin（IL）-6， nuclear transcription factor（NF）-κB1， peroxisome proliferator-activated receptor α（PPARα）， and tumor necrosis factor（TNF）， thus improving the symptoms of diseases related to spleen-lung Qi deficiency syndrome. ConclusionThis study established a UPLC-Q-TOF-MS/MS for rapid characterization and identification of chemical components in the decoction of Renshen Wuweizi Tang， expanding the understanding of the material composition of this formula， and found that 7 components might act on the key advantageous pharmacodynamic link "energy metabolism" through 6 targets to improve the related symptoms of spleen-lung Qi deficiency syndrome. This can provide a reference for the subsequent exploration of the material benchmark and mechanism of the famous classical formula.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Thyroid diseases are common clinical endocrine disorders， and their pathogenesis is generally considered to be closely related to genetic predisposition factors， immune system disorders， hormone levels， etc. Xiaoyaosan is widely used in the treatment of various thyroid diseases with excellent effects. This study summarized the relevant literature on the treatment of thyroid diseases with modified Xiaoyaosan prescriptions and their active ingredients from aspects such as theoretical analysis， clinical research， and mechanism research. Theoretical analysis revealed that Xiaoyaosan could not only disperse stagnated liver qi but also replenish deficient spleen Qi， which was consistent with the etiology and pathogenesis of thyroid diseases. Clinical studies found that Xiaoyaosan and its modified prescriptions could be widely used in the treatment of multiple thyroid diseases， such as hyperthyroidism， Hashimoto's thyroiditis， and thyroid nodules. Both the use of modified Xiaoyaosan alone and in combination with medications such as methimazole， propylthiouracil， and euthyrox could effectively improve patients' clinical symptoms. In the mechanism research， this study discovered that the whole formula of Xiaoyaosan and its modified prescriptions could inhibit inflammatory reactions， regulate immune balance， and delay liver damage during the treatment of thyroid diseases. The research on Xiaoyaosan for treating thyroid diseases mainly focused on thyroid cancer， autoimmune thyroiditis， hyperthyroidism， and hypothyroidism. The mechanisms of action mainly involved promoting cell apoptosis， inhibiting cell proliferation and migration， arresting the cell cycle， and regulating thyroid hormone levels. In conclusion， this study systematically combs and summarizes the research status of Xiaoyaosan in treating thyroid diseases through literature retrieval， aiming to provide new perspectives and new ideas for the prevention and treatment of thyroid diseases with traditional Chinese medicine.

Objective To investigate the combined effect of berberine （BBR） and fluconazole （FLC） on FLC-tolerant Candida albicans in vitro. Methods The sensitivity of 8 strains of Candida albicans to FLC was assessed by determining their minimal inhibitory concentration （MIC） using broth microdilution method. FLC-tolerant strains were screened from FLC-sensitive strains by disk diffusion assay. The effect of BBR combined with FLC on FLC-tolerant Candida albicans was investigated by disk diffusion assay. Results All eight strains of Candida albicans exhibited sensitivity to FLC, with minimal inhibitory concentration （MIC₅₀） values below 0.5 μg/ml. Strains Y0109, 9821, 7879, 7654, and 9296 displayed colony growth in the inhibition zone after 48 h of constant temperature incubation, indicating FLC tolerance. When strains Y0109 and 9821 were subjected to a combination of BBR and FLC, the number of colonies within the inhibition zone decreased progressively with the increase of BBR concentration following a 48 h constant temperature culture. The inhibition zone became clear with the increasing of BBR concentration and increased with the increase of FLC loading, which showed a dose-dependent relationship. Conclusion The BBR combined with FLC demonstrated efficacy against FLC-tolerant strains.

OBJECTIVE To improve the efficiency and quality of dispensed oral drug management in the inpatient pharmacy， and ensure the safety of drug use in patients. METHODS SWOT （strength， weakness， opportunity， threat） analysis method was used to analyze the internal strengths and weaknesses， as well as the external opportunities and threats in the construction of a closed-loop management system for dispensed oral drugs in the inpatient pharmacy of our hospital， and propose improvement strategies. RESULTS & CONCLUSIONS A refined， full-process， closed-loop traceability management system for dispensed oral drugs in the inpatient pharmacies was successfully established， which is traceable in origin， trackable in destination， and accountable in responsibility. After the application of this system， the registration rate of dispensed drug information and the correctness rate of registration content both reached 100%. The proportion of overdue drug varieties in the same period of 2024 decreased by 77.78% compared to March 2020， the inventory volume decreased by 29.50% compared to the first quarter of 2020， the per-bed medication volume decreased by 32.14% compared to the first quarter of 2020； the average workload per post in the same period of 2023 increased by 49.09% compared to 2019， the dispensing accuracy rate reached 100%， and the improvement rate of quality control problem increased by 25.25% compared to 2021. This system effectively improves the safety and accuracy of dispensed oral drug management in the inpatient pharmacy.

BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression， which may contribute to the anti-inflammatory properties of vagus nerve stimulation （VNS）， whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation （tcVNS） in treating major depressive disorder （MDD） and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression， anxiety and sleep quality as well as the plasma levels of interleukin-6 （IL-6） and interleukin-10 （IL-10） in MDD patients， in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21， 2019 to April 17， 2024， 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group （n=23） and control group （n=22） using random number table method. All patients were treated with escitalopram. On this basis， study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation， and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment， Hamilton Depression Scale-17 item （HAMD-17） was used to assess depressive symptoms， and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score， anxiety/somatization subfactor score and insomnia subfactor score in both groups （Wald χ²=315.226， 495.481， 82.420， P<0.01）. After 4 weeks of treatment， HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group， with statistically significant differences （Wald χ²=4.967， 32.543， P<0.05 or 0.01）， while no statistically significant difference was found in the insomnia subfactor score between two groups （Wald χ²=0.819， P=0.366）. Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups （Wald χ²=21.792， 5.242， P<0.05 or 0.01）. Compared with baseline data， a reduction in plasma IL-6 levels was detected in both groups （Wald χ²=22.015， 6.803， P<0.01）， and an increase in plasma IL-10 levels was reported in study group （Wald χ²=5.118， P=0.024） after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms， anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally， it helps reduce plasma IL-6 levels and increase IL-10 levels. ［Funded by Shaanxi Provincial Key Research and Development Program-General Project （number， 2023-YBSF-185）， www.clinicaltrials.gov number， NCT04037111］