BACKGROUND:During bone remodeling,bone formation and bone resorption are spatially and temporally coordinated,involving intricate interactions between osteoclasts and osteoblasts.Isoginkgetin,a flavonoid found in Ginkgo biloba,has a wide range of anticancer activity and anti-reactive oxygen species activity;however,the effect of isoginkgetin on osteoclast differentiation is unknown.OBJECTIVE:To study the effect and mechanism of action of isoginkgetin on osteoclastogenesis.METHODS:In vitro studies were performed on mouse bone marrow-derived macrophages,and cell counting kit-8 cytotoxicity assay was used to detect the effect of isoginkgetin on cell viability of bone marrow-derived macrophages.Macrophage colony-stimulating factor and receptor activator of nuclear factor kappa-B ligand were used to induce the differentiation of bone marrow-derived macrophages to osteoclasts.Network pharmacology and molecular docking and molecular dynamics simulations were used to predict the processes and targets of the effects of isoginkgetin on the differentiation of osteoclasts.Tartrate-resistant acid phosphatase staining and F-actin staining were used to detect the effects of isoginkgetin on the differentiation and function of osteoclasts.Western blot and RT-PCR were used to detect the effects of isoginkgetin on the expression of genes and proteins related to osteoclast differentiation,reactive oxygen species,and PI3K/AKT pathways.Fluorescent probes were used to detect cellular and mitochondrial reactive oxygen species levels.Flow cytometry technology was used to detect reactive oxygen species levels in cells.RESULTS AND CONCLUSION:(1)Network pharmacology results showed that isoginkgetin affected osteoporosis mainly through the PI3K-AKT pathway and cellular response to drugs and hypoxia,and GSK3β,ESR1,MCL1 and CCNA2 were the key targets.(2)Cell counting kit-8 and tartrate-resistant acid phosphatase staining results showed that isoginkgetin at 8 μmol/L had the most significant inhibitory effect on osteoclastogenesis in vitro,and F-actin results showed that isoginkgetin inhibited osteoclast cytoskeletal actin ring formation in a concentration-dependent manner.(3)Molecular dynamics simulations showed that isoginkgetin bound well to osteoclastogenesis marker proteins(NFATc1,c-Fos,CTSK,and MMP9).Western blot and RT-PCR results indicated that isoginkgetin inhibited the expression of osteoclastogenesis marker proteins and genes(NFATc1,c-Fos,CTSK,and MMP9).(4)Western blot results showed that isoginkgetin inhibited the phosphorylation level of PI3K/AKT/GSK3β and suppressed osteoclastogenesis by activating the PI3K-AKT-GSK3β pathway.(5)The results of reactive oxygen species assay showed that isoginkgetin significantly reduced receptor activator of nuclear factor kappa-B ligand-induced cellular and mitochondrial reactive oxygen species production,and inhibited the differentiation of bone marrow-derived macrophages to osteoclasts.

By consulting herbal texts， medical records， formula collections， and other relevant literature from various historical periods， as well as modern and contemporary research materials， different aspects of the historical evolution of Zijingpi， including its name， origin， scientific name verification， medicinal part， genuine producing areas， harvesting， processing， and preparation， properties and flavors， and primary indications， were systematically reviewed and verified， providing a basis for the development of famous classical formula preparations containing this medicinal material. According to the textual research， Cercis chinensis was first recorded under the name "Zijingmu" in the Rihuazi Bencao from the Five Dynasties period. From the Song Dynasty to the Qing Dynasty， it was known by various names such as "Zijing"， "Zijingpi"， and "Zijingmupi". In modern and contemporary times， it has been officially named "Zijingpi"， with aliases such as "Mantiaohong"， "Zihuashu"， and "Qingminghua". Historically， the mainstream source of Zijingpi was the dried bark of Cercis chinensis Bunge， a species of the legume family. However， there were also instances of confusion with the Lythraceae plant Lagerstroemia indica L. The producing areas of Zijingpi have no special geographical limitation， and the plant is currently distributed throughout most parts of China. There were no special requirements for harvesting time in ancient times， while modern records indicate harvesting time in spring， summer， and autumn. Ancient processing methods were rarely recorded， with only mentions of stir-frying Zijingpi. Modern practice mostly uses the raw material medicinally. Modern standards prefer it to be "dry， long strips， and thick". The functions of Zijingpi， mainly to promote blood circulation， relieve strangury， and detoxify， have remained consistent from ancient to modern times. Based on the textual research findings， it is recommended that when developing and exploiting the famous classical formulas containing Zijingpi， the bark of C. chinensis should be selected as the source. The processing method should be chosen according to the formula requirements， and if no specific requirements are indicated， it is suggested to use the raw material medicinally.

BACKGROUND:During bone remodeling,bone formation and bone resorption are spatially and temporally coordinated,involving intricate interactions between osteoclasts and osteoblasts.Isoginkgetin,a flavonoid found in Ginkgo biloba,has a wide range of anticancer activity and anti-reactive oxygen species activity;however,the effect of isoginkgetin on osteoclast differentiation is unknown.OBJECTIVE:To study the effect and mechanism of action of isoginkgetin on osteoclastogenesis.METHODS:In vitro studies were performed on mouse bone marrow-derived macrophages,and cell counting kit-8 cytotoxicity assay was used to detect the effect of isoginkgetin on cell viability of bone marrow-derived macrophages.Macrophage colony-stimulating factor and receptor activator of nuclear factor kappa-B ligand were used to induce the differentiation of bone marrow-derived macrophages to osteoclasts.Network pharmacology and molecular docking and molecular dynamics simulations were used to predict the processes and targets of the effects of isoginkgetin on the differentiation of osteoclasts.Tartrate-resistant acid phosphatase staining and F-actin staining were used to detect the effects of isoginkgetin on the differentiation and function of osteoclasts.Western blot and RT-PCR were used to detect the effects of isoginkgetin on the expression of genes and proteins related to osteoclast differentiation,reactive oxygen species,and PI3K/AKT pathways.Fluorescent probes were used to detect cellular and mitochondrial reactive oxygen species levels.Flow cytometry technology was used to detect reactive oxygen species levels in cells.RESULTS AND CONCLUSION:(1)Network pharmacology results showed that isoginkgetin affected osteoporosis mainly through the PI3K-AKT pathway and cellular response to drugs and hypoxia,and GSK3β,ESR1,MCL1 and CCNA2 were the key targets.(2)Cell counting kit-8 and tartrate-resistant acid phosphatase staining results showed that isoginkgetin at 8 μmol/L had the most significant inhibitory effect on osteoclastogenesis in vitro,and F-actin results showed that isoginkgetin inhibited osteoclast cytoskeletal actin ring formation in a concentration-dependent manner.(3)Molecular dynamics simulations showed that isoginkgetin bound well to osteoclastogenesis marker proteins(NFATc1,c-Fos,CTSK,and MMP9).Western blot and RT-PCR results indicated that isoginkgetin inhibited the expression of osteoclastogenesis marker proteins and genes(NFATc1,c-Fos,CTSK,and MMP9).(4)Western blot results showed that isoginkgetin inhibited the phosphorylation level of PI3K/AKT/GSK3β and suppressed osteoclastogenesis by activating the PI3K-AKT-GSK3β pathway.(5)The results of reactive oxygen species assay showed that isoginkgetin significantly reduced receptor activator of nuclear factor kappa-B ligand-induced cellular and mitochondrial reactive oxygen species production,and inhibited the differentiation of bone marrow-derived macrophages to osteoclasts.

OBJECTIVE To investigate the stability and compatibility of butorphanol， nicardipine， urapidil， and tirofiban. METHODS A micro-infusion pump was used to simulate the infusion process. Samples were collected in real time from the needle tip at 0， 2， 4， 6， and 8 h after mixing of the four drugs. The appearance， pH， and number of insoluble particles were examined. The contents of butorphanol， nicardipine， urapidil， and tirofiban were determined using the ultra-high-performance liquid chromatography method. RESULTS Within 8 hours， all mixed solutions remained clear and transparent， with no visible turbidity， precipitation， color change， or gas generation. The pH fluctuation ranged from 0.02 to 0.09， both within 0.1 pH units. The number of insoluble particles ≥10 μm in size in each compatibility solution was ≤9， and the number of insoluble particles ≥25 μm was ≤2， meeting the requirements of the 2025 edition of the Chinese Pharmacopoeia （Volume Ⅳ）. The relative percentage contents of butorphanol， nicardipine， urapidil， and tirofiban at 8 hours after compatibility mixing ranged from 92.38% to 113.40%. CONCLUSIONS Within 8 hours under simulated clinical micro-infusion pump infusion conditions， the stability and compatibility of the mixed solution containing butorphanol， nicardipine， urapidil， and tirofiban were satisfactory.

Abstract Traditional Chinese medicine (TCM) auscultation has a long history, and with advancements in equipment and analytical methods, the quantitative analysis of auscultation parameters has determined. However, the complexity and diversity of auscultation, along with variations in devices, analytical methods, and applications, bring challenges to its standardization and deeper application. This review presents the advancements in auscultation equipment and systems, auscultation characteristic parameters, and their application in the diagnosis of pulmonary diseases and syndromes over the past 10 years, while also exploring the progress and challenges of current digital research of auscultation. This review also proposes the establishment of standardized protocols for the collection and analysis of auscultation data, the incorporation of advanced artificial intelligence (AI) auscultation analysis methods, and an exploration of the diagnostic utility of auscultatory features in pulmonary diseases and syndromes, so as to provide more precise decision support for intelligent diagnosis of pulmonary diseases and syndromes

ObjectiveTo investigate the change in the expression of magnesium transporter 1 （MagT1） in peripheral blood CD8⁺ T cells in patients with chronic hepatitis B virus （HBV） infection， as well as the correlation of serum Mg²⁺ and MagT1 with HBV DNA load. MethodsA total of 102 patients with HBV infection who were admitted to Tangshan Workers’ Hospital from January 2022 to December 2023 were enrolled， and a case-control study was conducted. According to the stage of disease progression， the subjects were divided into chronic hepatitis B group with 40 patients， compensated liver cirrhosis group with 32 patients， and hepatocellular carcinoma group with 30 patients， and 32 healthy volunteers matched by age and sex were enrolled as normal control group. The serum concentration of Mg²⁺ was measured； RT-qPCR was used to measure the mRNA expression level of MagT1 in CD8⁺ T cells and serum HBV DNA load； flow cytometry was used to measure the expression levels of programmed death-1 （PD-1）， T-cell immunoglobulin and mucin-domain containing-3 （Tim-3）， and natural killer cell group 2D （NKG2D） on the surface of CD8⁺ T cells. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the SNK-q test was used for comparison between two groups； the chi-square test was used for comparison of categorical data between groups； a Pearson linear correlation analysis was used to investigate the correlation between the mRNA expression level of MagT1 and other related indicators. ResultsThere were significant differences in the serum level of Mg²⁺ and the mRNA expression level of MagT1 between the normal control group， the chronic hepatitis B group， the compensated liver cirrhosis group， and the hepatocellular carcinoma group （F=29.014 and 145.578， both P<0.001）. The Pearson correlation analysis showed that the serum level of Mg²⁺ and the mRNA expression level of MagT1 were positively correlated with HBV DNA load （r=0.335 and 0.394， both P<0.05）. The hepatocellular carcinoma group had the highest levels of PD-1 and Tim-3， followed by the compensated liver cirrhosis group， the chronic hepatitis B group， and the normal control group； the normal control group had the highest level of NKG2D， followed by the chronic hepatitis B group， the compensated liver cirrhosis group， and the hepatocellular carcinoma group （all P<0.001）. The Pearson correlation analysis showed that the mRNA expression level of MagT1 was negatively correlated with PD-1 and Tim-3 （r=-0.643 and -0.640， both P<0.05） and was positively correlated with NKG2D （r=0.655， P<0.05）. ConclusionThere is a reduction in the mRNA expression level of MagT1 in peripheral blood CD8⁺ T cells in patients with HBV infection， which is positively correlated with serum HBV DNA load. The reduction in the expression of MagT1 may contribute to CD8⁺ T cell exhaustion by impairing Mg²⁺ influx， manifesting as the upregulation of PD-1 and Tim-3 and the downregulation of NKG2D.

Objective:To investigate the impact of olanzapine and risperidone on the cognitive function, sensory gating function and clinical symptoms of patients with first-episode schizophrenia(FES).Additionally, to analyze the correlation between sensory gating inhibitory deficits and cognitive impairment in FES patients.Methods:A total of 71 FES patients were selected in the Third People's Hospital of Zhongshan City from March 2023 to March 2024, and 60 healthy controls were recruited during the same period.The FES patients were divided into olanzapine group and risperidone group by random number table.Olanzapine group was treated with variable doses of olanzapine(10-20 mg/d), and risperidone group was treated with variable doses of risperidone(3-6 mg/d).The MATRICS consensus cognitive battery(MCCB) was used to evaluate the cognitive function of the patients, P50 index was measured by auditory paired condition-stimulus paradigm, and the efficacy was evaluated by positive and negative syndrome scale(PANSS) score reduction rate before and after 6 weeks of treatment.Healthy controls were assessed cognitive function only once with P50.SPSS 25.0 software was used for data processing. Perform statistical analysis using paired sample t-test, Wilcoxon signed rank test, independent sample t-test, Mann Whitney U test, χ2 test and generalized linear model. Results:Before treatment, the S2 amplitude of FES (1.74 (0.91, 2.79) μV) was higher than that of healthy controls (1.70 (1.04, 2.71) μV) (Wald χ2=4.483, P=0.034), the S2/S1 ratio of FES (0.58 (0.43, 0.78)) was higher than that of healthy controls (0.41 (0.31, 0.57)) (Wald χ2=10.909, P=0.001), and the difference of FES amplitude of S1-S2 was (1.22 (0.43, 1.92) μV) was lower than that of healthy controls (2.23 (1.54, 3.07) μV) (Wald χ2=17.679, P<0.001). There was no significant difference in PANSS, MCCB and P50 between olanzapine group and risperidone group before treatment (all P>0.05). After treatment, there was no significant difference in response rate between the two groups ( χ2=0.059, P=0.808), the PANSS scores were lower than those before treatment, the MCCB test results were higher than those before treatment (both P<0.05), and the P50 results were not statistically significant different compared with those before treatment (both P>0.05). The generalized linear model showed that the S1, S2 amplitude of the P50 had positive impact on the connection test score in the MCCB test ( β=0.466, P=0.020; β=0.879, P=0.009), other indicators were not found to have an impact on the test scores of the MCCB test (all P>0.05). Conclusion:Olanzapine and risperidone can significantly improve the cognitive function of FES, but the improvement of sensory gating deficits is limited. The pathogenic mechanism of sensory gating inhibitory deficits in FES may be different from that of cognitive dysfunction.

Objective:To study the characteristics of thyroid-associated ophthalmopathy (TAO) clinical trials based on WHO International Clinical Trials Registry Platform (ICTRP).Methods:The WHO ICTRP database was searched from their inception to October 25, 2024.Data including the basic registration information, study type, study design, study stage, intervention measures and outcomes were extracted, and a descriptive analysis of the included trials was performed using bibliometric method.Results:A total of 288 trials were identified, the number of registrations for TAO interventional clinical trials was on the rise.Among them, 13 trials without key registration information, 93 without intervention, 2 with non-TAO subjects, 28 without control group, and 4 with duplicate study registration numbers or extension studies were excluded.Finally, 142 intervention trials were included in this study.The top three in registration numbers were China (44 trials), the United States (40 trials), and Europe (31 trials), and most of them were single-center studies (99 trials, accounting for 69.7%). For study design, 131 trials were randomized controlled trials, and 122 trials reported its masking method.Main stage of the trials was phase Ⅲ (31 trials, accounting for 21.8%). Drug treatments (121 trials, accounting for 85.2%) were the main intervention measures, and most of them were monoclonal antibody drugs (55 trials). Clinical activity score (81 trials) and exophthalmia (80 trials) were the commonly used outcome measures.Conclusions:The number of registrations for TAO interventional clinical trials is on the rise, with monoclonal antibody drugs as the main intervention measures.However, issues such as the limited registration number, uneven distribution of countries/regions, incomplete information, and low quality of study design remain to be addressed.Researchers should raise the awareness of registration and design of clinical trials, deepen international and interregional cooperation, improve the review and tracking mechanism of clinical trial registration platforms, and promote the high-quality development of TAO clinical trials.

Objective:To investigate the clinical manifestation, therapy, and prognosis of Susac syndrome and enhance the understanding of this disease.Methods:A case summary was made.The clinical data of two siblings with Susac syndrome treated at Children′s Medical Center, Peking University First Hospital in January 2024 were summarized.Reported cases of pediatric Susac syndrome were reviewed.Results:The onset of the disease in the two siblings was at the age of 3.00 and 6.75 years, with recurrent headaches, tinnitus, hearing loss and encephalopathy symptoms.Cranial magnetic resonance imaging showed multiple cerebral microbleeding and microinfarction lesions, " snowball like" in the corpus callosum and diffuse white matter edema in the brain.Audiometry revealed sensorineural hearing loss.In one case, ophthalmic fluorescein angiography revealed ischemic changes due to branch retinal artery occlusions.No pathogenic variants were detected in gene testing.This child was diagnosed with Susac syndrome, and the symptoms were improved after treatment with Corticosteroids and Rituximab.No relapse was observed during the 9-month follow-up.A total of 20 pediatric cases of Susac syndrome were retrieved, including 18 reported previously and 2 cases from this study.There were 2 boys and 18 girls, with the age of onset ranging from 2.5 to 17.0 years.The common initial symptoms included headache (19 cases), vertigo and tinnitus or hearing loss (9 cases), and vision impairment or visual field defect (4 cases). The symptoms were improved after immunotherapy.Conclusions:With a low incidence, Susac syndrome is rare in children and difficult to diagnose.There may be a genetic predisposition in such disease.Early diagnosis and immunotherapy can low the relapse and improve the prognosis.

Purpose To investigate the clinicopathological features,immunophenotypic profile,differential diag-noses,and prognostic implications of liver metastatic solid pseudopapillary neoplasm(LMSPN).Methods A retro-spective analysis was conducted on the clinicopathological features,immunohistochemical profile,and clinical outcomes of of 15 cases of LMSPN cases,supplemented by a literature review.Results Of the 15 patients,12 were female and 3 were male,with a mean age of 43 years(range 25-67 years).Multiple hepatic lesions were observed in 9 cases,some of which were accompanied by abdominal or omental metastasis.The tumors exhibited a cystic-solid appearence on gross examination,ranging from 0.5 to 15 cm in diameter.Histologically,the tumors showed typical cystic-solid and pseudopapillary areas,with tumor cells arranged around small blood vessels forming characteristic pseudopapillary structures.Tumor cells exhibited relatively uniform morphology,however,some cases presented with tumor necrosis(5/15),cytologic/nuclear atypia(4/15),mitotic figures(5/15),lymphovascular invasion(6/15),perineural inva-sion(3/15),and lymph node metastasis(2/15).Immunohistochemically,tumor cells showed variable expression ofβ-catenin,LEF1,vimentin,CD10,α1-ACT,PR,E-cadherin,NSE,CD56,Syn and Ki67.Notably,the nuclear ex-pression level of Ki67 and PR were significantly associated with prognosis(P＜0.05).β-catenin,LEF1,PR,and Ki67 were predominantly expressed in the nuclei,while markers such as CKpan,CgA,Hep Par-1,Arginase-1,CK7,and CK19 were negative or only weakly expressed.Follow-up data were available for 11 patients(range 10-157 months).Four patients died of widespread hepatic and abdominal metastases,while 7 remained alive.Conclusion The liver is the most most frequent site of distant metastasis for solid pseudopapillary neoplasms of the pancreas.High expression of Ki67 and PR is associated with unfavorable prognosis in LMSPN.