ObjectiveTo evaluate the effects of phases on the pharmacokinetic behavior of seven components from Banxia Xiexintang（BXT） in normal rats by investigating and comparing their pharmacokinetic profiles in different phase samples. MethodsThe phase separation of BXT was carried out by centrifugation-dialysis method， and three phase samples were obtained， including the precipitated phase（PP）， colloidal phase（CP） and true solution phase（TP）. A total of 24 male SD rats were randomly divided into BXT， PP， CP and TP groups（n=6）. The BXT group was gavaged at a dose of 24.1 g·kg^-1（calculated by the dosage of raw materials）. After proper treatments， PP， CP and TP groups were administrated at the same dose as that of BXT group， respectively. Blood was collected from each group at set time points after gavage of BXT and the phase samples. The contents of 7 components（baicalin， wogonoside， wogonin， berberine， palmatine， ammonium glycyrrhizinate and isoliquiritin） in rat plasma were determined by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）， and the pharmacokinetic parameters of each component were analyzed by DAS 2.0. ResultsThe peak concentration of baicalin was the highest among the blood-entered components in each group， followed by wogonoside. The results of the concentration-time curves and pharmacokinetic parameters of the 7 components showed that the area under the concentration-time curve（AUC） of isoliquiritin in the BXT group was the highest， followed by that in the CP group. AUC values of baicalin， wogonoside， wogonin and ammonium glycyrrhizinate in the BXT group were similar to those of the CP group， and AUC of palmatine in the BXT group was similar to that of the PP group. The elimination half-life（t_1/2） values of baicalin and wogonoside in the BXT group was the longest， the t_1/2 values of ammonium glycyrrhizinate and berberine were similar to those of the CP group， and the t_1/2 of palmatine was similar to that of the PP group. The t_1/2 of wogonin was the longest in the PP group， and the t_1/2 of isoliquiritin was the longest in the TP group was the longest， which was similar to that in the PP group. Except for isoliquiritin， the other 6 components showed double peaks in the concentration-time curve of the PP group， indicating that the above components might be reabsorbed through the enterohepatic circulation in vivo， which resulted in the maintenance of high plasma concentrations for a long time， and consequently exhibited sustained-release properties. ConclusionThe pharmacokinetic characteristics of the components in different phases were different， and the CP phase may be the effective phase from the perspective of the pharmacological action of BXT. Compared with the BXT group， the in vivo action times of some components in the CP and PP groups were prolonged. The study explores the phase differences of traditional Chinese medicine（TCM） compound decoction in the aspect of pharmacokinetics， and verifies that the phase states from TCM compound decoction will affect the pharmacokinetic behaviors of the active components， which may consequently lead to the difference in in vivo effects.

ObjectiveTo evaluate the effects of phases on the pharmacokinetic behavior of seven components from Banxia Xiexintang（BXT） in normal rats by investigating and comparing their pharmacokinetic profiles in different phase samples. MethodsThe phase separation of BXT was carried out by centrifugation-dialysis method， and three phase samples were obtained， including the precipitated phase（PP）， colloidal phase（CP） and true solution phase（TP）. A total of 24 male SD rats were randomly divided into BXT， PP， CP and TP groups（n=6）. The BXT group was gavaged at a dose of 24.1 g·kg^-1（calculated by the dosage of raw materials）. After proper treatments， PP， CP and TP groups were administrated at the same dose as that of BXT group， respectively. Blood was collected from each group at set time points after gavage of BXT and the phase samples. The contents of 7 components（baicalin， wogonoside， wogonin， berberine， palmatine， ammonium glycyrrhizinate and isoliquiritin） in rat plasma were determined by ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）， and the pharmacokinetic parameters of each component were analyzed by DAS 2.0. ResultsThe peak concentration of baicalin was the highest among the blood-entered components in each group， followed by wogonoside. The results of the concentration-time curves and pharmacokinetic parameters of the 7 components showed that the area under the concentration-time curve（AUC） of isoliquiritin in the BXT group was the highest， followed by that in the CP group. AUC values of baicalin， wogonoside， wogonin and ammonium glycyrrhizinate in the BXT group were similar to those of the CP group， and AUC of palmatine in the BXT group was similar to that of the PP group. The elimination half-life（t_1/2） values of baicalin and wogonoside in the BXT group was the longest， the t_1/2 values of ammonium glycyrrhizinate and berberine were similar to those of the CP group， and the t_1/2 of palmatine was similar to that of the PP group. The t_1/2 of wogonin was the longest in the PP group， and the t_1/2 of isoliquiritin was the longest in the TP group was the longest， which was similar to that in the PP group. Except for isoliquiritin， the other 6 components showed double peaks in the concentration-time curve of the PP group， indicating that the above components might be reabsorbed through the enterohepatic circulation in vivo， which resulted in the maintenance of high plasma concentrations for a long time， and consequently exhibited sustained-release properties. ConclusionThe pharmacokinetic characteristics of the components in different phases were different， and the CP phase may be the effective phase from the perspective of the pharmacological action of BXT. Compared with the BXT group， the in vivo action times of some components in the CP and PP groups were prolonged. The study explores the phase differences of traditional Chinese medicine（TCM） compound decoction in the aspect of pharmacokinetics， and verifies that the phase states from TCM compound decoction will affect the pharmacokinetic behaviors of the active components， which may consequently lead to the difference in in vivo effects.

The orientation of the acetabular cup in hip joint anteroposterior radiograph is a key factor in evaluating the postoperative outcomes of total hip arthroplasty (THA). Currently, measurement of the acetabular cup anteversion angle primarily relies on manual drawing of auxiliary lines by orthopedic surgeons and calculations using scientific calculators. This study proposes an automated computer-aided measurement method for the acetabular cup anteversion angle based on hip joint anteroposterior radiograph. The proposed method segments hip prosthesis images using an improved Otsu algorithm, identifies feature points at the acetabular cup opening by combining circle-fitting theory and the cup's geometric characteristics, and fits an ellipse to the cup opening to calculate the anteversion angle. A total of 104 hip joint anteroposterior radiographs, including 71 right-sided and 81 left-sided prostheses, were analyzed. Two orthopedic surgeons independently measured the postoperative anteversion angles, and the results were compared with computer-generated measurements for correlation analysis. Spearman and Pearson correlation analyses demonstrated significant correlations between the proposed method and manual measurements for both the right group ( r = 0.795, P < 0.01) and the left group ( r = 0.859, P < 0.01). This method provides a reliable reference for orthopedic surgeons to assess postoperative prognosis.
Humans ; Acetabulum/anatomy & histology* ; Arthroplasty, Replacement, Hip/methods* ; Algorithms ; Hip Prosthesis ; Hip Joint/diagnostic imaging* ; Radiography ; Image Processing, Computer-Assisted/methods*

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Objective:This report presents the initial outcomes of endoscopic intermuscular dissection (EID), a novel technique introduced by our team for the diagnostic resection of early rectal cancer, focusing on the postoperative status of the vertical margins.Methods:On January 26, 2024, a patient with early rectal cancer (cT1-2N0M0) underwent Endoscopic Intermuscular Dissection. The EID procedure consists of six steps: (1) mucosal incision; (2) submucosal dissection; (3) superficial muscular layer incision; (4) intermuscular dissection; (5) complete tumor removal; (6) wound management.Results:The patient was a 70-year-old male with rectal cancer (cT1-2N0M0). The tumor was located on the left anterior wall of the rectum, approximately 9 cm from the anal margin, and measured 20mm in size. The dissection rate was 2.68 mm2/minute, and the total duration of the surgery was 109 minutes. The patient was successfully discharged on the fifth day after surgery. Pathological examination of the post-endoscopic surgery specimen revealed pT1b, with negative vertical margins. Follow-up after more than one month showed good recovery with no complications such as bleeding, perforation, infection, or stricture occurring. Colonoscopy indicated the presence of a granulation tissue suggestive of inflammation.Conclusion:Endoscopic Intermuscular Dissection for the diagnostic resection of early rectal cancer is potentially safe and may achieve negative vertical margins.

AIM:To investigate of the effect of Shenqifuzheng injection(SFI)combined with PD-L1 antibody on tumor immune microenvironment and its efficacy.METHODS:A subcutaneous transplanta-tion tumor model for B16F10-LUC melanoma was created.The expression of Ki67,CD31,CD8,CD16,CD163,FOXP3,LY6C,LY6G with labeling antibodies was used to detect CD8+T cells,Treg cells,NK cells,MDSCs cells,centrocytes,and granulocytes in the tumor tissues via immunohistochemistry.Flow cy-tometry was used to measure the ratios of CD11c+,IA/IE+,and CD80+cells in splenic tissue,as well as the ratios of CD8+T,CD4+T,and Treg cells in tumor tissue.Additionally,granulocyte count and NK cell expression were analyzed.RESULTS:The immuno-histochemistry results indicate that the drug admin-istration group effectively suppressed tumor angio-genesis and cell proliferation,while decreasing the expression level of immunosuppressive cytokines CD4+T cells,Treg cells,MDSCs and centroblasts.Ad-ditionally,CD8 and NK cell infiltration was promot-ed compared to the control group.The results of the flow analysis demonstrated a significant in-crease in the expression level of CD8+T cells within tumor tissues,as well as inhibition of CD4+T,Treg,and DC cell infiltration within the spleen in the drug administration group.Additionally,the tumor volume analysis indicated that the drug administra-tion group effectively inhibited tumor growth.The flow results illustrate that the group administering treatment exhibited significant increases in CD8+T cell expression levels in tumor tissue and DC cells in the spleen.Furthermore,the treatment effec-tively inhibited the infiltration of CD4+T and Treg cells.The results also indicate that the treatment significantly reduced tumor growth,with the tumor inhibition rate being better with PD-L1 antibody alone than with the SFI group.Additionally,combin-ing drugs resulted in superior results compared to the PD-L1 antibody group alone.CONCLUSION:SFI combined with a PD-L1 antibody can have synergis-tic anti-tumor effects,potentially enhancing DC cell infiltration and promoting T cell activation.Immu-nohistochemistry results indicate a positive impact on the tumor immune microenvironment.

As a pathological vasodilation disease,intracranial aneurysm is an important cause of hemorrhagic stroke,and the specific mechanism of intracranial aneurysm formation is not very clear.The rupture of intracranial aneurysms often causes subarachnoid hemorrhage,leaving patients with severe sequelae and even death.Multiple morphological indicators based on aneurysm neck formation are important for assessing aneurysm stability and rupture risk.With the development of technology,the combination of neck-related parameters of intracranial aneurysms and clinical information of patients to make comprehensive diagnosis and treatment decisions is helpful for the accurate assessment of intracranial aneurysms and the further exploration of automated auxiliary evaluation systems.In this article,the authors reviewed the measurement of intracranial aneurysm neck-related parameters and their clinical applications in recent years and summarized and analyzed a variety of computer-aided aneurysm neck segmentation algorithms,hoping to provide a reference for future research on the accurate measurement and application of intracranial aneurysms and to provide more scientific and accurate morphological quantitative information for the formulation of clinical diagnosis and treatment plans.

Objective To discuss the efficacy and safety of transarterial chemoembolization(TACE)and hepatic arterial infusion chemotherapy(HAIC)combined with tyrosine kinase inhibitors(TKI)and immune checkpoint inhibitors(ICI)for advanced hepatocellular carcinoma(HCC).Methods A total of 101 patients with unresectable HCC,who were admitted to the Affiliated Cancer Hospital of Harbin Medical University of China between January 2021 and October 2022 to receive treatment,were enrolled in this study.Of the 101 patients,50 received TACE+TKI+ICI therapy(TACE+TKI+ICI group)and 51 received HAIC+TKI+ICI therapy(HAIC+TKI+ICI group).The overall survival(OS)and the progression-free survival(PFS)were compared between the two groups,and the adverse events were analyzed to assess the safety of the therapeutic scheme.Results The median PFS in the TACE+TKI+ICI group was 12.0 months,which in the HAIC+TKI+ICI group was 11.0 months(P=0.030).The median OS was not achieved in the TACE+TKI+ICI group,which in the HAIC+TKI+ICI group was 14.6 months(P=0.005).The most common adverse effects in the TACE+TKI+ICI group were the elevation of total bilirubin(46.0％)and hepatic function injury(26.0％),which in the HAIC+TKI+ICI group were the decrease of albumin level(62.7％),fatigue(39.2％),and gastrointestinal reactions(31.4％).Conclusion For the treatment of advanced HCC,the therapeutic scheme of TACE+TKI+ICI has a better long-term survival benefits and the therapeutic scheme of HAIC+TKI+ICI can better maintain the liver function reserve of the patients.Neither therapeutic scheme shows any unexpected toxicity,and both therapeutic schemes have high clinical safety.(J Intervent Radiol,2024,33:543-548)

Objective To evaluate the efficacy and safety of mFOLFOX-based hepatic arterial infusion chemotherapy(HAIC)combined with tyrosine kinase inhibitors(TKIs)and immune checkpoint inhibitors(ICIs)in the treatment of advanced hepatocellular carcinoma(HCC)complicated by portal vein tumor thrombus(PVTT).Methods The clinical data of 37 patients with HCC complicated by PVTT,who received mFOLFOX-based HAIC combined with TKI and ICI at the Department of Intervention,Affiliated Cancer Hospital of Harbin Medical University of China between January 2021 and January 2023,were retrospective analyzed.The primary endpoint was the objective remission rate of PVTT response,and the secondary endpoints included the 6-month survival rate,one-year survival rate,and overall survival(OS).The treatment-related adverse events and complications were evaluated.PVTT response was assessed using ITK-SNAP software,life table was used to calculate 6-month and one-year survival,Kaplan-Meier survival curve was used to assess overall OS,and logistic regression analysis and Cox regression analysis were used to analyze the risk factors associated with PVTT response and OS.Results Of the 37 patients,complete resolution of PVTT volume(CR)was obtained in 7(18.92％),and reduction of PVTT volume over 50％was obtained in 21(56.76％).The objective remission rate(ORR)of PVTT was 75.68％.The 6-month survival rate was 89％,the one-year survival rate was 66％,and the median OS was 15.8 months.Univariate analysis indicated that cavernous degeneration of portal vein(CTPV)was correlated with PVTT response(P=0.010).The Child-Pugh score(P=0.010)and the presence of PVTT response(P=0.004)to treatment were the important factors for predicting OS.Multivariate analysis revealed that the preoperative volume of cancer thrombus(P=0.033),cavernous degeneration of portal vein(P=0.007)were the important factors for predicting the PVTT response,and the Child-Pugh score(P=0.035)and the presence of PVTT response during treatment(P=0.015)were the important factors for predicting OS.The most common adverse reactions related to HAIC were oxaliplatin-related pain(n=30,80％)and thrombocytopenia(n=22,59％),among them 10patients(27％)developed grade Ⅲ painand4patients(11％)developed grade Ⅲ thrombocytopenia.The pain could be alleviated by slowing down the pump velocity and corresponding pain relief treatment.The targeted therapy and immunotherapy-related common adverse reaction was hand and foot reactions(n=16,45％),among them 6 patients(16％)developed grade Ⅲ hand and foot reactions.Conclusion FOLFOX-based HAIC combined with targeted therapy and immunotherapy can obtain a 75.68％ORR of PVTT,which provides more therapeutic options for intrahepatic tumors.

The microbiome plays a role in the development of lower urinary tract diseases, but the impact of viruses on these conditions remains unclear. In recent years, research has emerged demonstrating a potential link between viruses and lower urinary tract diseases, including bladder cancer, prostate cancer, and overactive bladder. In this paper, the research of the correlation between viruses and lower urinary tract diseases and the related mechanisms were reviewed.