1.Effects of borneol on pharmacodynamics and pharmacokinetics of Corydalis saxicola total alkaloids in depression model rats
Yu YE ; Guoliang DAI ; Huaxi HANG ; Meishuang YU ; Yiran WANG ; Xuewen SHAO ; Wenzheng JU
China Pharmacy 2025;36(1):30-36
OBJECTIVE To investigate the effects of borneol on pharmacodynamic and pharmacokinetic effects of Corydalis saxicola total alkaloids in depression model rats. METHODS Thirty male SD rats were divided into blank control group, negative control group, positive control group (fluoxetine 10 mg/kg, i.g.), single drug group (C. saxicola total alkaloids 210 mg/kg, i.g.) and combined drug group (C. saxicola total alkaloids 210 mg/kg+borneol 50 mg/kg, i.g.) according to the random number table method, with 6 rats in each group. By lipopolysaccharide (LPS) induction modeling, except blank control group (no model and no administration) received intraperitoneal injection of the same amount of normal saline, the rats in the other groups were intraperitoneally injected with LPS once a day to establish a rat model of depression. After 1 week of modeling, each administration group was given relevant drug intragastrically according to the corresponding dose, and blank control group and negative control group (without drug treatment) were administered intragastrically with an equal volume of solvent to dissolve the drug; continued modeling while administering the drug. After two weeks of continuous administration, the effects of C. saxicola total alkaloids versus the combination of C. saxicola total alkaloids and borneol on the behavior of depressed rats were tested by behavioral experiments; the levels of tumor necrosis factor-α, interleukin-1β and interleukin-6 in rats were determined; the histopathological changes of the hippocampus of rats were observed. Blood sample was collected from the orbit at different time points after administration on the 15th day, and the upper plasma was obtained. Ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry was established for the simultaneous determination of dehydrocarvedine, tetrahydropalmatine, coptisine, palmatine, jatrorrhizine, berberine, berberrubine and epiberberine in rat plasma. The average plasma concentration-time curve was depicted, the area under the curve (AUC) was calculated, and the pharmacokinetic parameters were analyzed by DAS 3.2.2 software. RESULTS Compared with blank control group, the negative control group had a decrease in body mass and sugar water preference rate, a decrease in the total distance of open field, a prolonged swimming immobility time, and a increased in the expression of inflammatory factors in serum (P<0.05); compared with negative control group, the single drug group and the combined drug group increased the preference rate of sugar water, increased the total distance of open field, shortened the time of swimming immobility, and decreased the expression of inflammatory factors in serum (P<0.05). There was no significant difference in the above indicators between the single drug group and the combined drug group in rats (P>0.05). Pharmacokinetic results showed that compared with single drug group, AUC0-t of coptisine, AUC0-t, AUC0-∞, tmax and cmax of jatrorrhizine, AUC0-t, AUC0-∞, t1/2 and cmax of berberrubine, and AUC0-t of epiberberine, cmax of dehydrocarvedine, cmax of palmatine were significantly increased in combined drug group, but there was no significant difference, indicating that borneol didn’t have a significant effect on the efficacy of Corydalis saxicola nigra at this dose. CONCLUSIONS Both C. saxicola total alkaloids alone and in combination with borneol can improve depression-like behavior in depression model rats, reduce serum inflammatory cytokine levels, and protect hippocampal neurons. Compared with the use of Corydalis saxicola base alone, the combination with borneol do not show significant pharmacodynamic differences, bu can improve the absorption of coptisine, jatrorrhizine in model rats.
2.Effect of Borneol on Pharmacodynamics,Pharmacokinetics and Brain Tissue Distribution of Main Active Ingredients of Jiaotaiwan in Depression Model Rats
Meishuang YU ; Guoliang DAI ; Huaxi HANG ; Yu YE ; Yiran WANG ; Xuewen SHAO ; Wenzheng JU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(24):18-27
ObjectiveTo investigate the pharmacodynamics, pharmacokinetics and brain distribution of seven main components of Jiaotaiwan alone and Jiaotaiwan combined with borneol in lipopolysaccharide(LPS)-induced depression rats. MethodRats were randomly divided into the control group, model group, fluoxetine group(10 mg·kg-1), Jiaotaiwan group(1.5 g·kg-1) and combination group(1.5 g·kg-1 of Jiaotaiwan+0.05 g·kg-1 of borneol), with 8 rats in each group. Except for the control group, the depression model was established by intraperitoneal injection of LPS for 7 consecutive days, and each group was given the corresponding drugs or the same volume of pure water by gavage for 14 consecutive days. The behavioral indicators and levels of serum inflammatory factors[interleukin-1β(IL-1β), IL-6 and tumor necrosis factor-α(TNF-α)] of rats in each group were compared. The morphological changes of hippocampal neurons were observed by hematoxylin-eosin(HE) and Nissl staining. After the behavioral tests of sucrose preference, open field and forced swimming were completed, blood samples were collected from Jiaotaiwan group and combination group at the set time points after gavage, the contents of seven components in plasma were determined by ultra performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS/MS), and the pharmacokinetic parameters of each component were analyzed by DAS 3.2.2. Brains were rapidly removed on ice after blood collection was completed, and UPLC-QqQ-MS/MS was used to compare the content changes of the 7 components in brain tissue. ResultCompared with the control group, rats in the model group showed decreased sucrose preference rate and total distance of open field, prolonged swimming immobility time, and increased expression of inflammatory factors in serum(P<0.01). Compared with the model group, the sucrose preference rate and total distance of open field were increased, and the swimming immobility time was shortened in the rats of each administration group, and the expression of inflammatory factors in serum was decreased in rats from Jiaotaiwan group and combination group(P<0.05, P<0.01). The results of HE and Nissl staining showed that Jiaotaiwan group and combination group had a certain protective effect on hippocampal neurons. The pharmacokinetic results showed that compared with Jiaotaiwan group, the area under the curve(AUC0-t, AUC0-∞), peak concentration(Cmax) and the average steady-state plasma concentration(Cav) of berberine and epiberberine in the combination group were increased(P<0.05, P<0.01), AUC0-t, AUC0-∞, mean residence time(MRT0-∞) and Cav of coptisine were significantly increased(P<0.05, P<0.01), Cmax of jatrorrhizine increased significantly(P<0.05), but the pharmacokinetic changes of the seven alkaloids were consistent. The results of brain tissue distribution showed that compared with Jiaotaiwan group, the contents of jatrorrhizine, epiberberine, coptisine, palmatine and berberine in the brain tissue of combination group were increased(P<0.05, P<0.01), the content of magnoflorine increased and that of berberrubine decreased, but the difference was not statistically significant. ConclusionJiaotaiwan alone or combined with borneol can improve the depression-like behavior of rats, reduce the levels of serum inflammatory factors, improve the pathological damage of hippocampus, and have antidepressant effect. Compared with Jiaotaiwan alone, the combination of Jiaotaiwan and borneol can increase the exposure of multiple active components of Jiaotaiwan in the plasma and brain tissue of rats, improve its bioavailability, promote its absorption, and improve the brain targeting of the drug, which is more conducive to the antidepressant effect of Jiaotaiwan.
3.Research progress in MRI-based radiomics for predicting the efficacy of transcatheter arterial chemoembolization for hepatocellular carcinoma
Journal of Interventional Radiology 2024;33(1):90-94
Hepatocellular carcinoma(HCC)is the fifth most common malignant tumor in the world and it is characterized by clinically insidious onset and high mortality rate.As a preferred treatment method for patients with moderate and advanced HCC,transcatheter arterial chemoembolization(TACE)has many advantages such as reducing tumor load and relieving patient pain,but the selection of the patients who may get benefits from TACE treatment remains a challenging issue.Therefore,it is essential to predict the efficacy of TACE.At present,various methods including clinical laboratory testing,imaging method,genetic-molecular method,etc.have been used to predict the therapeutic efficacy of TACE.Imaging prediction has the advantages of high visualization and strong interpretability,and MRI functional imaging sequence can better demonstrate the details of the lesion.Radiomics,as an emerging imaging field,can complement or even replace tumor biopsy by quantifying the tumor phenotypic variation.This paper aims to make a review concerning the correlation between the imaging radiomics and the prediction of TACE efficacy in patients with HCC,and to discuss whether MRI imaging radiomics can be used as a valid and reproducible method for predicting TACE efficacy for HCC.(J Intervent Radiol,2024,32:90-94)
4.Pharmacokinetics of Total Alkaloids of Corydalis saxicola in Depression Model Rats
Huaxi HANG ; Meishuang YU ; Yu YE ; Qian HUANG ; Yiran WANG ; Xuewen SHAO ; Peiyao CHEN ; Yang CAO ; Guoliang DAI ; Wenzheng JU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(14):175-183
ObjectiveTo investigate the effect of total alkaloids of Corydalis saxicola on a rat model of lipopolysaccharide(LPS)-induced depression, as well as the pharmacokinetic characteristics of 8 of its major components. MethodTwenty-four male SD rats were randomly divided into normal group, model group, fluoxetine group(10 mg·kg-1) and total alkaloids of C. saxicola group(210 mg·kg-1), with 6 rats in each group. In addition to the normal group, the rats were injected intraperitoneally with LPS to establish the inflammation model of depression, and the drug administration was started 1 week after modeling, and the administration groups were gavaged according to the corresponding dose, and the normal and model groups were intragastric administration with equal volume of distilled water, and the administration was performed along with the modeling. After two weeks of continuous administration, the effect of total alkaloids of C. saxicola on the behavior of depressed rats were tested by sucrose preference, forced swimming and open field experiments, the levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β and IL-6 in serum of rats were determined by enzyme-linked immunosorbent assay(ELISA), the histopathological changes of rat hippocampus were observed by hematoxylin-eosin(HE) staining. After the last administration, blood was collected from orbit according to the set time, and ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-QqQ-MS) was established to simultaneously detect the concentrations of dehydrocavidine, tetrahydropalmatine, coptisine, palmatine, jatrorrhizine, berberine, berberrubine and epiberberine in plasma, and drug-time curves were drawn. The pharmacokinetic parameters were analyzed by DAS 2.0 software. ResultCompared with the normal group, the model group exhibited a decrease in sucrose preference rate, total distance traveled in the open field, as well as an increase in swimming immobility time and serum inflammatory factor expression(P<0.01). In contrast, compared with the model group, rats in each administration group showed an increase in sucrose preference rate and total distance traveled in the open field, a decrease in swimming immobility time, and a reduction in serum inflammatory factor expression(P<0.05, P<0.01). Additionally, HE staining results revealed that neurons in the hippocampus of rats from the model group were characterized by loss, disorganization and residual vacuoles, whereas those from the total alkaloids of C.saxicola group displayed an increase in number with orderly arrangement and clear cytoplasm. Pharmacokinetic results showed that the time to peak(tmax) and half-life(t1/2) of the 8 active ingredients were 0.19-2.06 h and 3.71-8.70 h after continuous administration of total alkaloids of C. saxicola. Among them, the area under the curve(AUC0-∞) of tetrahydropalmatine was the highest and the t1/2 was the shortest, and the AUC0-∞ of coptisine, palmatine, jatrorrhizine, berberine, berberrubine and epiberberine were low. The curves of dehydrocavidine, coptisine, palmatine, berberine and epiberberine showed obvious double peak phenomenon. ConclusionTotal alkaloids of C. saxicola can improve the depression-like behavior of rats, inhibit the expression of inflammatory factors in serum, improve the pathological injury of hippocampus, and has the antidepressant effect. Meanwhile, the effective site is absorbed quickly and eliminated slowly in the depressed model rats, and the efficacy is maintained for a long time.
5.Clinical application of reconstruction of pelvic floor with pedunculated omentum flap combined with basement membrane biological products in pelvic exenteration with sacrococcygeal bone
Guoliang CHEN ; Yulu WANG ; Qifeng XIE ; Ning SU ; Zhiguo WANG ; Guoyi SHAO ; Jian ZHANG
Chinese Journal of Gastrointestinal Surgery 2024;27(11):1162-1167
Objective:To introduce the experience of reconstructing the pelvic floor with a pedicled large omental flap combined with a basement membrane biological mesh in combined pelvic organ resection for locally advanced or locally recurrent rectal cancer combined with sacrococcygeal resection, and to discuss the feasibility, safety, and near-term therapeutic efficacy of this technique.Methods:For patients with sacrococcygeal resection of combined pelvic organs, a basement membrane mesh was used to rebuild the pelvic floor with a pedicled greater omentum flap to isolate the abdominopelvic cavity. The main operation was to pull the greater omentum, which preserved the double vascular arches, to the pelvic floor to cover the pelvic floor, and then the mesh was used to cover the posterior peritoneal defect and pelvic inlet with absorbable sutures of 2-0 or thicker.Results:In this study, a retrospective cohort study was used to collect clinical data through the China Rectal Cancer Combined Pelvic Organs Resections Case Database. Twenty patients with locally advanced or locally recurrent rectal cancer without extra-pelvic metastasis or only oligometastases underwent combined pelvic organ and sacrococcygeal resection in the Department of Anal and Intestinal Surgery of the Second Affiliated Hospital of the Naval Military Medical University during the period of July 1, 2022, to June 30, 2023, and 10 patients underwent simple basement membrane resection with a simple basement membrane. Among them, the pelvic floor were reconstructed by basement membrane mesh alone in 10 cases (mesh only group), and 10 cases were reconstructed the pelvic floor by pedicled large omental flap combined with basement membrane mesh (omental flap-combined mesh group). The recent outcomes of the two groups of patients were studied comparatively. Comparison of baseline data and intraoperative conditions between the two groups showed no statistically significant differences (all P>0.05); the drain removal time in the omental flap-combined mesh group was 26.7 (19-42) days, which was shorter than that in the mesh only group, which was 40.4 (24-56) days ( U=4.125, P=0.001); The empty pelvis healing time in the omental flap-combined mesh group was 29.4 (23~43) days, which was shorter than that of 42.2 (27~58) days in the mesh-only group ( U=4.043, P=0.001); the differences were all statistically significant. The postoperative complication rate of grade ≥III in the omental flap-combined mesh group was 1/10, which was lower than that of 6/10 in the mesh-only group; the difference was not statistically significant when comparing the two groups ( P = 0.057). Follow-up ended on 09/30/2023, with a median follow-up of 9.5 (3-15) months in 20 patients, and all 20 cases survived during the follow-up period, with no tumor recurrence at the surgical site. Conclusion:In locally advanced or locally recurrent rectal cancer undergoing combined pelvic organ resection with sacrococcygeal, compared with reconstruction of the pelvic floor by basement membrane mesh alone, reconstruction of the pelvic floor and isolation of the abdominopelvic cavity by a pedicled greater omentum flap combined with a basement membrane mesh is safe and feasible.
6.Clinical application of reconstruction of pelvic floor with pedunculated omentum flap combined with basement membrane biological products in pelvic exenteration with sacrococcygeal bone
Guoliang CHEN ; Yulu WANG ; Qifeng XIE ; Ning SU ; Zhiguo WANG ; Guoyi SHAO ; Jian ZHANG
Chinese Journal of Gastrointestinal Surgery 2024;27(11):1162-1167
Objective:To introduce the experience of reconstructing the pelvic floor with a pedicled large omental flap combined with a basement membrane biological mesh in combined pelvic organ resection for locally advanced or locally recurrent rectal cancer combined with sacrococcygeal resection, and to discuss the feasibility, safety, and near-term therapeutic efficacy of this technique.Methods:For patients with sacrococcygeal resection of combined pelvic organs, a basement membrane mesh was used to rebuild the pelvic floor with a pedicled greater omentum flap to isolate the abdominopelvic cavity. The main operation was to pull the greater omentum, which preserved the double vascular arches, to the pelvic floor to cover the pelvic floor, and then the mesh was used to cover the posterior peritoneal defect and pelvic inlet with absorbable sutures of 2-0 or thicker.Results:In this study, a retrospective cohort study was used to collect clinical data through the China Rectal Cancer Combined Pelvic Organs Resections Case Database. Twenty patients with locally advanced or locally recurrent rectal cancer without extra-pelvic metastasis or only oligometastases underwent combined pelvic organ and sacrococcygeal resection in the Department of Anal and Intestinal Surgery of the Second Affiliated Hospital of the Naval Military Medical University during the period of July 1, 2022, to June 30, 2023, and 10 patients underwent simple basement membrane resection with a simple basement membrane. Among them, the pelvic floor were reconstructed by basement membrane mesh alone in 10 cases (mesh only group), and 10 cases were reconstructed the pelvic floor by pedicled large omental flap combined with basement membrane mesh (omental flap-combined mesh group). The recent outcomes of the two groups of patients were studied comparatively. Comparison of baseline data and intraoperative conditions between the two groups showed no statistically significant differences (all P>0.05); the drain removal time in the omental flap-combined mesh group was 26.7 (19-42) days, which was shorter than that in the mesh only group, which was 40.4 (24-56) days ( U=4.125, P=0.001); The empty pelvis healing time in the omental flap-combined mesh group was 29.4 (23~43) days, which was shorter than that of 42.2 (27~58) days in the mesh-only group ( U=4.043, P=0.001); the differences were all statistically significant. The postoperative complication rate of grade ≥III in the omental flap-combined mesh group was 1/10, which was lower than that of 6/10 in the mesh-only group; the difference was not statistically significant when comparing the two groups ( P = 0.057). Follow-up ended on 09/30/2023, with a median follow-up of 9.5 (3-15) months in 20 patients, and all 20 cases survived during the follow-up period, with no tumor recurrence at the surgical site. Conclusion:In locally advanced or locally recurrent rectal cancer undergoing combined pelvic organ resection with sacrococcygeal, compared with reconstruction of the pelvic floor by basement membrane mesh alone, reconstruction of the pelvic floor and isolation of the abdominopelvic cavity by a pedicled greater omentum flap combined with a basement membrane mesh is safe and feasible.
7.Efficacy and safety of transcatheter arterial infusion chemotherapy with gemcitabine and nab-paclitaxel regimen for advanced pancreatic cancer
Zhewei ZHANG ; Hui ZENG ; Jiaping ZHENG ; Jun LUO ; Liwen GUO ; Fei CAO ; Weiren LIANG ; Guoliang SHAO
Journal of Interventional Radiology 2024;33(5):512-515
Objective To evaluate the clinical efficacy and safety of transcatheter arterial infusion with gemcitabine and nab-paclitaxel(GN)as first-line therapy in treating patients with advanced pancreatic cancer.Methods The clinical data of a total of 50 patients with advanced pancreatic cancer,who were treated with transcatheter arterial infusion chemotherapy with GN regimen at the Zhejiang Cancer Hospital of China between January 2016 and December2020,were collected The objective effective rate(ORR),progression-free survival(PFS),overall survival(OS)and treatment-related toxic reactions were analyzed.Results A total of 236 times of transcatheter arterial infusion chemotherapy were carried out in the 50 patients,with an average perfusion procedure of 4.72 times per patient.Complete remission(CR)was obtained in 0 patient,partial remission(PR)in 16 patients,and stable disease(SD)in 21 patients.The ORR was 32%,the median PFSwas5.1 months,and the OS was 9.8 months.The main adverse events included neutropenia,thrombocytopenia,vomiting,nausea,fatigue,etc.Conclusion For patients with advanced pancreatic cancer,transcatheter arterial infusion chemotherapy with GN regimen carries good short-term efficacy and safety,it can improve patient's PFS and OS to a certain extent.(J Intervent Radiol,2024,33:512-515)
8.The guiding value of CTA in the treatment of vascular embolization in emergency pelvic fracture hemorrhage
Fangye WU ; Hongwei XU ; Hui ZENG ; Guoliang SHAO
China Modern Doctor 2024;62(22):46-49
Objective To investigate the guiding value of computed tomography angiography(CTA)in the treatment of vascular embolization in patients with emergency pelvic fracture hemorrhage.Methods From June 2019 to June 2023,67 patients with emergency pelvic fracture hemorrhage were selected from General Hospital Medical Communities of Shaoxing Second Hospital.All patients underwent CTA and digital subtraction angiography(DSA),and the application value of CTA was evaluated using the results of DSA as the gold standard.Results CTA examination showed that 66 patients had vascular injury,bleeding or injury of 167 vessels.DSA examination showed that 66 patients had vascular injury,bleeding or injury of 186 vessels.The detection rate of CTA for positive cases was 97.0%,and the detection rate for vascular injury was 82.8%.The positive predictive value of CTA was 92.2%,the negative predictive value was 97.1%,the sensitivity was 82.8%,and the specificity was 98.8%.Conclusion The diagnostic results of CTA examination for emergency pelvic fracture hemorrhage are highly consistent with DSA,which can provide an important reference for the formulation of treatment plans for patients.
9.The mean Hounsfield unit range acquired from different slices produces superior predictive accuracy for pyonephrosis in obstructive uropathy
Baoxing HUANG ; Guoliang LU ; Yang ZHAO ; Weichao TU ; Yuan SHAO ; Dawei WANG ; Danfeng XU
Investigative and Clinical Urology 2024;65(3):286-292
Purpose:
To determine the non-contrast computer tomography imaging features of pyonephrosis and evaluate the predictive value of Hounsfield units (HUs) in different hydronephrotic region slices.
Materials and Methods:
We retrospectively reviewed data from patients with hydronephrosis who had renal-ureteral calculi. All patients were categorized into pyonephrosis and simple hydronephrosis groups. Baseline characteristics, the mean HU values in the maximal hydronephrotic region (uHU) slice, and the range of uHU in different slices (△uHU) were compared between the two groups. Univariate and multivariate analyses were performed to identify risk factors for pyonephrosis.
Results:
Among the 181 patients enrolled in the current study, 71 patients (39.2%) were diagnosed with pyonephrosis. The mean dilated pelvis surface areas were comparable between patients with pyonephrosis and simple hydronephrosis (822.61 ㎟ vs.877.23 ㎟ , p=0.722). Collecting system debris (p=0.022), a higher uHU (p=0.038), and a higher △uHU (p<0.001) were identified as independent risk factors for pyonephrosis based on multivariate analysis. The △uHU sensitivity and specificity were 88.7% and 86.4%, respectively, at a cutoff value of 6.56 (p<0.001), whereas the sensitivity and specificity for detecting pyonephrosis at a uHU cutoff value of 7.96 was 50.7% and 70.9%, respectively (p=0.003).
Conclusions
Non-contrast computer tomography was shown to accurately distinguish simple hydronephrosis from pyonephrosis in patients with obstructive uropathy. Evaluation of the △uHU in different slices may be more reliable than the uHU acquired from a single slice in predicting pyonephrosis.
10.Single-cell transcriptomic analysis of tumor heterogeneity and intercellular networks in human urothelial carcinoma
Xingwei JIN ; Qizhang WANG ; Fangxiu LUO ; Junwei PAN ; Tingwei LU ; Yang ZHAO ; Xiang ZHANG ; Enfei XIANG ; Chenghua ZHOU ; Baoxing HUANG ; Guoliang LU ; Peizhan CHEN ; Yuan SHAO
Chinese Medical Journal 2023;136(6):690-706
Background::Heterogeneity of tumor cells and the tumor microenvironment (TME) is significantly associated with clinical outcomes and treatment responses in patients with urothelial carcinoma (UC). Comprehensive profiling of the cellular diversity and interactions between malignant cells and TME may clarify the mechanisms underlying UC progression and guide the development of novel therapies. This study aimed to extend our understanding of intra-tumoral heterogeneity and the immunosuppressive TME in UC and provide basic support for the development of novel UC therapies.Methods::Seven patients with UC were included who underwent curative surgery at our hospital between July 2020 and October 2020. We performed single-cell RNA sequencing (scRNA-seq) analysis in seven tumors with six matched adjacent normal tissues and integrated the results with two public scRNA-seq datasets. The functional properties and intercellular interactions between single cells were characterized, and the results were validated using multiplex immunofluorescence staining, flow cytometry, and bulk transcriptomic datasets. All statistical analyses were performed using the R package with two-sided tests. Wilcoxon-rank test, log-rank test, one-way analysis of variance test, and Pearson correlation analysis were used properly.Results::Unsupervised t-distributed stochastic neighbor embedding clustering analysis identified ten main cellular subclusters in urothelial tissues. Of them, seven urothelial subtypes were noted, and malignant urothelial cells were characterized with enhanced cellular proliferation and reduced immunogenicity. CD8 + T cell subclusters exhibited enhanced cellular cytotoxicity activities along with increased exhaustion signature in UC tissues, and the recruitment of CD4 + T regulatory cells was also increased in tumor tissues. Regarding myeloid cells, coordinated reprogramming of infiltrated neutrophils, M2-type polarized macrophages, and LAMP3 + dendritic cells contribute to immunosuppressive TME in UC tissues. Tumor tissues demonstrated enhanced angiogenesis mediated by KDR + endothelial cells and RGS5 +/ACTA2 + pericytes. Through deconvolution analysis, we identified multiple cellular subtypes may influence the programmed death-ligand 1 (PD-L1) immunotherapy response in patients with UC. Conclusion::Our scRNA-seq analysis clarified intra-tumoral heterogeneity and delineated the pro-tumoral and immunosuppressive microenvironment in UC tissues, which may provide novel therapeutic targets.

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